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Sample records for elegans model system

  1. Modeling the C. elegans nematode and its environment using a particle system.

    Science.gov (United States)

    Rönkkö, Mauno; Wong, Garry

    2008-07-21

    A particle system, as understood in computer science, is a novel technique for modeling living organisms in their environment. Such particle systems have traditionally been used for modeling the complex dynamics of fluids and gases. In the present study, a particle system was devised to model the movement and feeding behavior of the nematode Caenorhabditis elegans in three different virtual environments: gel, liquid, and soil. The results demonstrate that distinct movements of the nematode can be attributed to its mechanical interactions with the virtual environment. These results also revealed emergent properties associated with modeling organisms within environment-based systems.

  2. An in vivo C. elegans model system for screening EGFR-inhibiting anti-cancer drugs.

    Directory of Open Access Journals (Sweden)

    Young-Ki Bae

    Full Text Available The epidermal growth factor receptor (EGFR is a well-established target for cancer treatment. EGFR tyrosine kinase (TK inhibitors, such as gefinitib and erlotinib, have been developed as anti-cancer drugs. Although non-small cell lung carcinoma with an activating EGFR mutation, L858R, responds well to gefinitib and erlotinib, tumors with a doubly mutated EGFR, T790M-L858R, acquire resistance to these drugs. The C. elegans EGFR homolog LET-23 and its downstream signaling pathway have been studied extensively to provide insight into regulatory mechanisms conserved from C. elegans to humans. To develop an in vivo screening system for potential cancer drugs targeting specific EGFR mutants, we expressed three LET-23 chimeras in which the TK domain was replaced with either the human wild-type TK domain (LET-23::hEGFR-TK, a TK domain with the L858R mutation (LET-23::hEGFR-TK[L858R], or a TK domain with the T790M-L858R mutations (LET-23::hEGFR-TK[T790M-L858R] in C. elegans vulval cells using the let-23 promoter. The wild-type hEGFR-TK chimeric protein rescued the let-23 mutant phenotype, and the activating mutant hEGFR-TK chimeras induced a multivulva (Muv phenotype in a wild-type C. elegans background. The anti-cancer drugs gefitinib and erlotinib suppressed the Muv phenotype in LET-23::hEGFR-TK[L858R]-expressing transgenic animals, but not in LET-23::hEGFR-TK[T790M-L858R] transgenic animals. As a pilot screen, 8,960 small chemicals were tested for Muv suppression, and AG1478 (an EGFR-TK inhibitor and U0126 (a MEK inhibitor were identified as potential inhibitors of EGFR-mediated biological function. In conclusion, transgenic C. elegans expressing chimeric LET-23::hEGFR-TK proteins are a model system that can be used in mutation-specific screens for new anti-cancer drugs.

  3. The role of mycelium production and a MAPK-mediated immune response in the C. elegans-Fusarium model system

    Science.gov (United States)

    Muhammed, Maged; Fuchs, Beth Burgwyn; WU, Michael P.; Breger, Julia; Coleman, Jeffrey J.; Mylonakis, Eleftherios

    2013-01-01

    Fusariosis is an emerging infectious complication of immune deficiency, but models to study this infection are lacking. The use of the soil nematode Caenorhabditis elegans as a model host to study the pathogenesis of Fusarium spp. was investigated. We observed that Fusarium conidia consumed by C. elegans can cause a lethal infection and result in more than 90% killing of the host within 120 hours, and the nematode had a significantly longer survival when challenged with Fusarium proliferatum compared to other species. Interestingly, mycelium production appears to be a major contributor in nematode killing in this model system, and C. elegans mutant strains with the immune response genes, tir-1 (encoding a protein containing a TIR domain that functions upstream of PMK-1) and pmk-1 (the homolog of the mammalian p38 MAPK) lived significantly shorter when challenged with Fusarium compared to the wild type strain. Furthermore, we used the C. elegans model to assess the efficacy and toxicity of various compounds against Fusarium. We demonstrated that amphotericin B, voriconazole, mancozeb, and phenyl mercury acetate significantly prolonged the survival of Fusarium-infected C. elegans, although mancozeb was toxic at higher concentrations. In conclusion, we describe a new model system for the study of Fusarium pathogenesis and evolutionarily preserved host responses to this important fungal pathogen. PMID:22225407

  4. Caenorhabditis elegans as a Model System for Studying Drug Induced Mitochondrial Toxicity.

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    Richard de Boer

    Full Text Available Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the mitochondrial DNA polymerase. For detailed investigation of the yet partially understood underlying mechanisms, the availability of a versatile model system is crucial. We therefore set out to develop the use of Caenorhabditis elegans to study drug induced mitochondrial toxicity. Using a combination of molecular-biological and functional assays, combined with a quantitative analysis of mitochondrial network morphology, we conclude that anti-retroviral drugs with similar working mechanisms can be classified into distinct groups based on their effects on mitochondrial morphology and biochemistry. Additionally we show that mitochondrial toxicity of antiretroviral drugs cannot be exclusively attributed to interference with the mitochondrial DNA polymerase.

  5. Caenorhabditis elegans as a model system for studying non-cell-autonomous mechanisms in protein-misfolding diseases

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    Carmen I. Nussbaum-Krammer

    2014-01-01

    Full Text Available Caenorhabditis elegans has a number of distinct advantages that are useful for understanding the basis for cellular and organismal dysfunction underlying age-associated diseases of protein misfolding. Although protein aggregation, a key feature of human neurodegenerative diseases, has been typically explored in vivo at the single-cell level using cells in culture, there is now increasing evidence that proteotoxicity has a non-cell-autonomous component and is communicated between cells and tissues in a multicellular organism. These discoveries have opened up new avenues for the use of C. elegans as an ideal animal model system to study non-cell-autonomous proteotoxicity, prion-like propagation of aggregation-prone proteins, and the organismal regulation of stress responses and proteostasis. This Review focuses on recent evidence that C. elegans has mechanisms to transmit certain classes of toxic proteins between tissues and a complex stress response that integrates and coordinates signals from single cells and tissues across the organism. These findings emphasize the potential of C. elegans to provide insights into non-cell-autonomous proteotoxic mechanisms underlying age-related protein-misfolding diseases.

  6. Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

    Science.gov (United States)

    Koch, Karoline; Havermann, Susannah; Büchter, Christian

    2014-01-01

    Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research. PMID:24895670

  7. Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

    Directory of Open Access Journals (Sweden)

    Karoline Koch

    2014-01-01

    Full Text Available Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research.

  8. C. elegans model of neuronal aging

    OpenAIRE

    Peng, Chiu-Ying; Chen, Chun-Hao; Hsu, Jiun-Min; Pan, Chun-Liang

    2011-01-01

    Aging of the nervous system underlies the behavioral and cognitive decline associated with senescence. Understanding the molecular and cellular basis of neuronal aging will therefore contribute to the development of effective treatments for aging and age-associated neurodegenerative disorders. Despite this pressing need, there are surprisingly few animal models that aim at recapitulating neuronal aging in a physiological context. We recently developed a C. elegans model of neuronal aging, and...

  9. Models of Caenorhabditis elegans infection by bacterial and fungal pathogens.

    Science.gov (United States)

    Powell, Jennifer R; Ausubel, Frederick M

    2008-01-01

    The nematode Caenorhabditis elegans is a simple model host for studying the relationship between the animal innate immune system and a variety of bacterial and fungal pathogens. Extensive genetic and molecular tools are available in C. elegans, facilitating an in-depth analysis of host defense factors and pathogen virulence factors. Many of these factors are conserved in insects and mammals, indicating the relevance of the nematode model to the vertebrate innate immune response. Here, we describe pathogen assays for a selection of the most commonly studied bacterial and fungal pathogens using the C. elegans model system.

  10. C. elegans as a model in developmental neurotoxicology.

    Science.gov (United States)

    Ruszkiewicz, Joanna A; Pinkas, Adi; Miah, Mahfuzur R; Weitz, Rebecca L; Lawes, Michael J A; Akinyemi, Ayodele J; Ijomone, Omamuyovwi M; Aschner, Michael

    2018-03-14

    Due to many advantages Caenorhabditis elegans (C. elegans) has become a preferred model of choice in many fields, including neurodevelopmental toxicity studies. This review discusses the benefits of using C. elegans as an alternative to mammalian systems and gives examples of the uses of the nematode in evaluating the effects of major known neurodevelopmental toxins, including manganese, mercury, lead, fluoride, arsenic and organophosphorus pesticides. Reviewed data indicates numerous similarities with mammals in response to these toxins. Thus, C. elegans studies have the potential to predict possible effects of developmental neurotoxicants in higher animals, and may be used to identify new molecular pathways behind neurodevelopmental disruptions, as well as new toxicants. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. A living model for obesity and aging research: Caenorhabditis elegans.

    Science.gov (United States)

    Shen, Peiyi; Yue, Yiren; Park, Yeonhwa

    2018-03-24

    Caenorhabditis elegans (C. elegans) is a free-living nematode that has been extensively utilized as an animal model for research involving aging and neurodegenerative diseases, like Alzheimer's and Parkinson's, etc. Compared with traditional animal models, this small nematode possesses many benefits, such as small body size, short lifespan, completely sequenced genome, and more than 65% of the genes associated with human disease. All these characteristics make this organism an ideal living system for obesity and aging studies. This review gives a brief introduction of C. elegans as an animal model, highlights some advantages of research using this model and describes methods to evaluate the effect of treatments on obesity and aging of this organism.

  12. Genetic screens in Caenorhabditis elegans models for neurodegenerative diseases

    NARCIS (Netherlands)

    Alvarenga Fernandes Sin, Olga; Michels, Helen; Nollen, Ellen A. A.

    2014-01-01

    Caenorhabditis elegans comprises unique features that make it an attractive model organism in diverse fields of biology. Genetic screens are powerful to identify genes and C. elegans can be customized to forward or reverse genetic screens and to establish gene function. These genetic screens can be

  13. Caenorhabditis elegans, a Biological Model for Research in Toxicology.

    Science.gov (United States)

    Tejeda-Benitez, Lesly; Olivero-Verbel, Jesus

    2016-01-01

    Caenorhabditis elegans is a nematode of microscopic size which, due to its biological characteristics, has been used since the 1970s as a model for research in molecular biology, medicine, pharmacology, and toxicology. It was the first animal whose genome was completely sequenced and has played a key role in the understanding of apoptosis and RNA interference. The transparency of its body, short lifespan, ability to self-fertilize and ease of culture are advantages that make it ideal as a model in toxicology. Due to the fact that some of its biochemical pathways are similar to those of humans, it has been employed in research in several fields. C. elegans' use as a biological model in environmental toxicological assessments allows the determination of multiple endpoints. Some of these utilize the effects on the biological functions of the nematode and others use molecular markers. Endpoints such as lethality, growth, reproduction, and locomotion are the most studied, and usually employ the wild type Bristol N2 strain. Other endpoints use reporter genes, such as green fluorescence protein, driven by regulatory sequences from other genes related to different mechanisms of toxicity, such as heat shock, oxidative stress, CYP system, and metallothioneins among others, allowing the study of gene expression in a manner both rapid and easy. These transgenic strains of C. elegans represent a powerful tool to assess toxicity pathways for mixtures and environmental samples, and their numbers are growing in diversity and selectivity. However, other molecular biology techniques, including DNA microarrays and MicroRNAs have been explored to assess the effects of different toxicants and samples. C. elegans has allowed the assessment of neurotoxic effects for heavy metals and pesticides, among those more frequently studied, as the nematode has a very well defined nervous system. More recently, nanoparticles are emergent pollutants whose toxicity can be explored using this nematode

  14. Gait modulation in C. elegans: An integrated neuromechanical model

    Directory of Open Access Journals (Sweden)

    Jordan Hylke Boyle

    2012-03-01

    Full Text Available Equipped with its 302-cell nervous system, the nematode Caenorhabditis elegans adapts its locomotion in different environments, exhibiting so-called swimming in liquids and crawling on dense gels. Recent experiments have demonstrated that the worm displays the full range of intermediate behaviors when placed in intermediate environments. The continuous nature of this transition strongly suggests that these behaviors all stem from modulation of a single underlying mechanism. Wepresent a model of C. elegans forward locomotion that includes a neuromuscular control system that relies on a sensory feedback mechanism to generate undulations and is integrated with a physical model of the body and environment. We find that the model reproduces the entire swim-crawl transition, as well as locomotion in complex and heterogeneous environments. This is achieved with no modulatory mechanism, except via the proprioceptive response to the physical environment. Manipulations of the model are used to dissect the proposed pattern generation mechanism and its modulation. The model suggests a possible role for GABAergic D-class neurons in forward locomotion and makes a number of experimentalpredictions, in particular with respect to nonlinearities in the model and to symmetry breaking between the neuromuscular systems on the ventral and dorsal sides of the body.

  15. The worm has turned--microbial virulence modeled in Caenorhabditis elegans.

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    Sifri, Costi D; Begun, Jakob; Ausubel, Frederick M

    2005-03-01

    The nematode Caenorhabditis elegans is emerging as a facile and economical model host for the study of evolutionarily conserved mechanisms of microbial pathogenesis and innate immunity. A rapidly growing number of human and animal microbial pathogens have been shown to injure and kill nematodes. In many cases, microbial genes known to be important for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity in nematodes. C. elegans has been used in mutation-based screening systems to identify novel virulence-related microbial genes and immune-related host genes, many of which have been validated in mammalian models of disease. C. elegans-based pathogenesis systems hold the potential to simultaneously explore the molecular genetic determinants of both pathogen virulence and host defense.

  16. Caenorhabditis elegans: a simple nematode infection model for Penicillium marneffei.

    Directory of Open Access Journals (Sweden)

    Xiaowen Huang

    Full Text Available Penicillium marneffei, one of the most important thermal dimorphic fungi, is a severe threat to the life of immunocompromised patients. However, the pathogenic mechanisms of P. marneffei remain largely unknown. In this work, we developed a model host by using nematode Caenorhabditis elegans to investigate the virulence of P. marneffei. Using two P. marneffei clinical isolate strains 570 and 486, we revealed that in both liquid and solid media, the ingestion of live P. marneffei was lethal to C. elegans (P<0.001. Meanwhile, our results showed that the strain 570, which can produce red pigment, had stronger pathogenicity in C. elegans than the strain 486, which can't produce red pigment (P<0.001. Microscopy showed the formation of red pigment and hyphae within C. elegans after incubation with P. marneffei for 4 h, which are supposed to be two contributors in nematodes killing. In addition, we used C. elegans as an in vivo model to evaluate different antifungal agents against P. marneffei, and found that antifungal agents including amphotericin B, terbinafine, fluconazole, itraconazole and voriconazole successfully prolonged the survival of nematodesinfected by P. marneffei. Overall, this alternative model host can provide us an easy tool to study the virulence of P. marneffei and screen antifungal agents.

  17. A Preliminary Study of the Application of a Model Animal-Caenorhabidity elegans' Exposure to a Low-Energy Ion Irradiation System

    International Nuclear Information System (INIS)

    Liu Xuelan; Cai Kezhou; Feng Huiyun; Xu An; Yuan Hang; Yu Zengliang

    2007-01-01

    Because of the lack of suitable animal models adapted to high vacuum stress in the low-energy ion implantation system, the bio-effects ion irradiation with an energy less than 50 keV on multi-cellular animal individuals have never been investigated so far. The nematode Caenorhabditis elegans has proved to be an excellent animal model used for the study of a broad spectrum of biological issues. The purpose of this work was to investigate the viability of this animal under ion irradiation. We studied the protection effects of glycerol and trehalose on the enhancement of nematodes' ability to bear the vacuum stress. The results showed that the survival of the nematodes was enhanced remarkably under long and slow desiccation, even without glycerol and trehalose. 15% glycerol showed a better anti-vacuum stress effect on the nematodes than trehalose did under short-time desiccation. Low-temperature pre-treatment or post-treatment of the samples had no obvious effect on the survival scored after argon ion irradiation. Moreover, little effect was induced by 15% glycerol- and vacuum-exposure on germ cell apoptosis, compared to the untreated control sample. It issuggested that such treatment would provide relatively low background for genotoxic evaluations with ion irradiation

  18. Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction.

    Science.gov (United States)

    Engleman, Eric A; Katner, Simon N; Neal-Beliveau, Bethany S

    2016-01-01

    Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH's effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system-dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine neurotransmission

  19. Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction

    Science.gov (United States)

    Engleman, Eric A.; Katner, Simon N.; Neal-Beliveau, Bethany S.

    2016-01-01

    Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH’s effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system–dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine

  20. A distance constrained synaptic plasticity model of C. elegans neuronal network

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    Badhwar, Rahul; Bagler, Ganesh

    2017-03-01

    Brain research has been driven by enquiry for principles of brain structure organization and its control mechanisms. The neuronal wiring map of C. elegans, the only complete connectome available till date, presents an incredible opportunity to learn basic governing principles that drive structure and function of its neuronal architecture. Despite its apparently simple nervous system, C. elegans is known to possess complex functions. The nervous system forms an important underlying framework which specifies phenotypic features associated to sensation, movement, conditioning and memory. In this study, with the help of graph theoretical models, we investigated the C. elegans neuronal network to identify network features that are critical for its control. The 'driver neurons' are associated with important biological functions such as reproduction, signalling processes and anatomical structural development. We created 1D and 2D network models of C. elegans neuronal system to probe the role of features that confer controllability and small world nature. The simple 1D ring model is critically poised for the number of feed forward motifs, neuronal clustering and characteristic path-length in response to synaptic rewiring, indicating optimal rewiring. Using empirically observed distance constraint in the neuronal network as a guiding principle, we created a distance constrained synaptic plasticity model that simultaneously explains small world nature, saturation of feed forward motifs as well as observed number of driver neurons. The distance constrained model suggests optimum long distance synaptic connections as a key feature specifying control of the network.

  1. Using Caenorhabditis elegans as a Model for Obesity Pharmacology Development.

    Science.gov (United States)

    Zheng, Jolene; Vasselli, Joseph R; King, Jason F; King, Michael L; We, Wenqian; Fitzpatrick, Zachary; Johnson, William D; Finley, John W; Martin, Roy J; Keenan, Michael J; Enright, Frederic M; Greenway, Frank L

    The Caenorhabditis elegans model is a rapid and inexpensive method to address pharmacologic questions. We describe the use of C. elegans to explore 2 pharmacologic questions concerning candidate antiobesity drugs and illustrate its potential usefulness in pharmacologic research: (1) to determine a ratio of betahistine-olanzapine that blocks the olanzapine-induced intestinal fat deposition (IFD) as detected by Nile red staining and (2) to identify the mechanism of action of a pharmaceutical candidate AB-101 that reduces IFD. Olanzapine (53 μg/mL) increased the IFD (12.1 ± 0.1%, P < 0.02), which was blocked by betahistine (763 μg/mL, 39.3 ± 0.01%, P < 0.05) in wild-type C. elegans (N2). AB-101 (1.0%) reduced the IFD in N2 (P < 0.05), increased the pharyngeal pumping rate (P < 0.05), and reversed the elevated IFD induced by protease inhibitors atazanavir and ritonavir (P < 0.05). AB-101 did not affect IFD in a ACS null mutant strain acs-4(ok2872) III/hT2[bli-4(e937) let-?(q782) qIs48](I;III) suggesting an involvement of the lipid oxidation pathway and an upregulation of CPT-1. Our studies suggest that C. elegans may be used as a resource in pharmacologic research. This article is intended to stimulate a greater appreciation of its value in the development of new pharmaceutical interventions.

  2. Modeling Behavioral Experiment Interaction and Environmental Stimuli for a Synthetic C. elegans

    Directory of Open Access Journals (Sweden)

    Andoni Mujika

    2017-12-01

    Full Text Available This paper focusses on the simulation of the neural network of the Caenorhabditis elegans living organism, and more specifically in the modeling of the stimuli applied within behavioral experiments and the stimuli that is generated in the interaction of the C. elegans with the environment. To the best of our knowledge, all efforts regarding stimuli modeling for the C. elegansare focused on a single type of stimulus, which is usually tested with a limited subnetwork of the C. elegansneural system. In this paper, we follow a different approach where we model a wide-range of different stimuli, with more flexible neural network configurations and simulations in mind. Moreover, we focus on the stimuli sensation by different types of sensory organs or various sensory principles of the neurons. As part of this work, most common stimuli involved in behavioral assays have been modeled. It includes models for mechanical, thermal, chemical, electrical and light stimuli, and for proprioception-related self-sensed information exchange with the neural network. The developed models have been implemented and tested with the hardware-based Si elegans simulation platform.

  3. Caenorhabditis elegans as a powerful alternative model organism to promote research in genetic toxicology and biomedicine.

    Science.gov (United States)

    Honnen, Sebastian

    2017-05-01

    In view of increased life expectancy the risk for disturbed integrity of genetic information increases. This inevitably holds the implication for higher incidence of age-related diseases leading to considerable cost increase in health care systems. To develop preventive strategies it is crucial to evaluate external and internal noxae as possible threats to our DNA. Especially the interplay of DNA damage response (DDR) and DNA repair (DR) mechanisms needs further deciphering. Moreover, there is a distinct need for alternative in vivo test systems for basic research and also risk assessment in toxicology. Especially the evaluation of combinational toxicity of environmentally present genotoxins and adverse effects of clinically used DNA damaging anticancer drugs is a major challenge for modern toxicology. This review focuses on the applicability of Caenorhabditis elegans as a model organism to unravel and tackle scientific questions related to the biological consequences of genotoxin exposure and highlights methods for studying DDR and DR. In this regard large-scale in vivo screens of mixtures of chemicals and extensive parallel sequencing are highlighted as unique advantages of C. elegans. In addition, concise information regarding evolutionary conserved molecular mechanisms of the DDR and DR as well as currently available data obtained from the use of prototypical genotoxins and preferential read-outs of genotoxin testing are discussed. The use of established protocols, which are already available in the community, is encouraged to facilitate and further improve the implementation of C. elegans as a powerful genetic model system in genetic toxicology and biomedicine.

  4. Impact of a Complex Food Microbiota on Energy Metabolism in the Model Organism Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Elena Zanni

    2015-01-01

    Full Text Available The nematode Caenorhabditis elegans is widely used as a model system for research on aging, development, and host-pathogen interactions. Little is currently known about the mechanisms underlying the effects exerted by foodborne microbes. We took advantage of C. elegans to evaluate the impact of foodborne microbiota on well characterized physiological features of the worms. Foodborne lactic acid bacteria (LAB consortium was used to feed nematodes and its composition was evaluated by 16S rDNA analysis and strain typing before and after colonization of the nematode gut. Lactobacillus delbrueckii, L. fermentum, and Leuconostoc lactis were identified as the main species and shown to display different worm gut colonization capacities. LAB supplementation appeared to decrease nematode lifespan compared to the animals fed with the conventional Escherichia coli nutrient source or a probiotic bacterial strain. Reduced brood size was also observed in microbiota-fed nematodes. Moreover, massive accumulation of lipid droplets was revealed by BODIPY staining. Altered expression of nhr-49, pept-1, and tub-1 genes, associated with obesity phenotypes, was demonstrated by RT-qPCR. Since several pathways are evolutionarily conserved in C. elegans, our results highlight the nematode as a valuable model system to investigate the effects of a complex microbial consortium on host energy metabolism.

  5. Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system.

    Science.gov (United States)

    Toth, Marton Lorant; Melentijevic, Ilija; Shah, Leena; Bhatia, Aatish; Lu, Kevin; Talwar, Amish; Naji, Haaris; Ibanez-Ventoso, Carolina; Ghose, Piya; Jevince, Angela; Xue, Jian; Herndon, Laura A; Bhanot, Gyan; Rongo, Chris; Hall, David H; Driscoll, Monica

    2012-06-27

    Caenorhabditis elegans is a powerful model for analysis of the conserved mechanisms that modulate healthy aging. In the aging nematode nervous system, neuronal death and/or detectable loss of processes are not readily apparent, but because dendrite restructuring and loss of synaptic integrity are hypothesized to contribute to human brain decline and dysfunction, we combined fluorescence microscopy and electron microscopy (EM) to screen at high resolution for nervous system changes. We report two major components of morphological change in the aging C. elegans nervous system: (1) accumulation of novel outgrowths from specific neurons, and (2) physical decline in synaptic integrity. Novel outgrowth phenotypes, including branching from the main dendrite or new growth from somata, appear at a high frequency in some aging neurons, but not all. Mitochondria are often associated with age-associated branch sites. Lowered insulin signaling confers some maintenance of ALM and PLM neuron structural integrity into old age, and both DAF-16/FOXO and heat shock factor transcription factor HSF-1 exert neuroprotective functions. hsf-1 can act cell autonomously in this capacity. EM evaluation in synapse-rich regions reveals a striking decline in synaptic vesicle numbers and a diminution of presynaptic density size. Interestingly, old animals that maintain locomotory prowess exhibit less synaptic decline than same-age decrepit animals, suggesting that synaptic integrity correlates with locomotory healthspan. Our data reveal similarities between the aging C. elegans nervous system and mammalian brain, suggesting conserved neuronal responses to age. Dissection of neuronal aging mechanisms in C. elegans may thus influence the development of brain healthspan-extending therapies.

  6. Caenorhabditis elegans as a Model for Toxic Effects of Nanoparticles: Lethality, Growth, and Reproduction.

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    Maurer, Laura L; Ryde, Ian T; Yang, Xinyu; Meyer, Joel N

    2015-11-02

    The nematode Caenorhabditis elegans is extensively utilized in toxicity studies. C. elegans offers a high degree of homology with higher organisms, and its ease of use and relatively inexpensive maintenance have made it an attractive complement to mammalian and ecotoxicological models. C. elegans provides multiple benefits, including the opportunity to perform relatively high-throughput assays on whole organisms, a wide range of genetic tools permitting investigation of mechanisms and genetic sensitivity, and transparent bodies that facilitate toxicokinetic studies. This unit describes protocols for three nanotoxicity assays in C. elegans: lethality, growth, and reproduction. This unit focuses on how to use these well-established assays with nanoparticles, which are being produced in ever-increasing volume and exhibit physicochemical properties that require alteration of standard toxicity assays. These assays permit a broad phenotypic assessment of nanotoxicity in C. elegans, and, when used in combination with genetic tools and other assays, also permit mechanistic insight. Copyright © 2015 John Wiley & Sons, Inc.

  7. Identification of Novel Candidate Tumor Suppressor Genes Using C. elegans as a Model

    National Research Council Canada - National Science Library

    Sternberg, Paul

    1999-01-01

    Molecular genetic analysis of the model organism Caenorhabditis elegans was used to identify and study mechanisms of action of negative regulators of tyrosine kinase/RAS mediated signal transduction...

  8. Identification of Novel Candidate Tumor Suppressor Genes Using C. elegans as a Model

    National Research Council Canada - National Science Library

    Sternberg, Paul

    1998-01-01

    Molecular genetic analysis of the model organism Caenorhabditis elegans was used to identify and study mechanisms of action of negative regulators of tyrosine kinase/RAS mediated signal transduction...

  9. C. elegans as a virulence model for E. coli strain 042

    OpenAIRE

    Kjærbo, Rasmus E. R.; Godballe, Troels; Hansen, Klaus G.; Petersen, Pernille D.; Tikander, Emil

    2010-01-01

    During the last decade the nematode Caenorhabditis elegans has been used to model the pathogenesis of several bacterial species. The emerging pathogen enteroaggregative Escherichia coli (EAEC) is a considerable cause of both acute and persistent diarrhea worldwide. Travellers to developing countries, immunocompromised people and young children are high-risk groups prone to infection. Virulence models using C. elegans might provide valuable information about the host-pathogen interactions whic...

  10. Interplay among Resistance Profiles, High-Risk Clones, and Virulence in the Caenorhabditis elegans Pseudomonas aeruginosa Infection Model.

    Science.gov (United States)

    Sánchez-Diener, Irina; Zamorano, Laura; López-Causapé, Carla; Cabot, Gabriel; Mulet, Xavier; Peña, Carmen; Del Campo, Rosa; Cantón, Rafael; Doménech-Sánchez, Antonio; Martínez-Martínez, Luis; Arcos, Susana C; Navas, Alfonso; Oliver, Antonio

    2017-12-01

    The increasing prevalence of nosocomial infections produced by multidrug-resistant (MDR) or extensively drug-resistant (XDR) Pseudomonas aeruginosa is frequently linked to widespread international strains designated high-risk clones. In this work, we attempted to decipher the interplay between resistance profiles, high-risk clones, and virulence, testing a large ( n = 140) collection of well-characterized P. aeruginosa isolates from different sources (bloodstream infections, nosocomial outbreaks, cystic fibrosis, and the environment) in a Caenorhabditis elegans infection model. Consistent with previous data, we documented a clear inverse correlation between antimicrobial resistance and virulence in the C. elegans model. Indeed, the lowest virulence was linked to XDR profiles, which were typically linked to defined high-risk clones. However, virulence varied broadly depending on the involved high-risk clone; it was high for sequence type 111 (ST111) and ST235 but very low for ST175. The highest virulence of ST235 could be attributed to its exoU + type III secretion system (TTSS) genotype, which was found to be linked with higher virulence in our C. elegans model. Other markers, such as motility or pigment production, were not essential for virulence in the C. elegans model but seemed to be related with the higher values of the statistical normalized data. In contrast to ST235, the ST175 high-risk clone, which is widespread in Spain and France, seems to be associated with a particularly low virulence in the C. elegans model. Moreover, the previously described G154R AmpR mutation, prevalent in ST175, was found to contribute to the reduced virulence, although it was not the only factor involved. Altogether, our results provide a major step forward for understanding the interplay between P. aeruginosa resistance profiles, high-risk clones, and virulence. Copyright © 2017 American Society for Microbiology.

  11. Characterization of the interaction between the human pathogen Listeria monocytogenes and the model host C. elegans

    DEFF Research Database (Denmark)

    Simonsen, Karina T.; Nielsen, Jesper S.; Hansen, Annie A.

    In nature, C. elegans lives in the soil and feeds on bacteria. This constant contact with soil-borne microbes suggests that nematodes must have evolved protective responses against pathogens which makes the worm an attractive host-pathogen model for exploring their innate immune response....... In addition, C. elegans is a promising model for the identification of novel virulence factors in various pathogens. A large number of human, animal, plant and insect pathogens have been shown to kill the worm, when C. elegans was allowed to feed on pathogens in stead of its normal laboratory diet [1......]. However, the mechanisms that lead to the shortened life span of the worm have been shown to be very different depending on the nature of the pathogen. Examples include Yersinia pestis, which forms a biofilm layer on the cuticle of C. elegans thus inhibiting feeding [2], enteropathogenic Escherichia coli...

  12. Caenorhabditis elegans as a model to study renal development and disease: sexy cilia.

    Science.gov (United States)

    Barr, Maureen M

    2005-02-01

    The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

  13. Inactivation of GABAA receptor is related to heat shock stress response in organism model Caenorhabditis elegans.

    Science.gov (United States)

    Camargo, Gabriela; Elizalde, Alejandro; Trujillo, Xochitl; Montoya-Pérez, Rocío; Mendoza-Magaña, María Luisa; Hernandez-Chavez, Abel; Hernandez, Leonardo

    2016-09-01

    The mechanisms underlying oxidative stress (OS) resistance are not completely clear. Caenorhabditis elegans (C. elegans) is a good organism model to study OS because it displays stress responses similar to those in mammals. Among these mechanisms, the insulin/IGF-1 signaling (IIS) pathway is thought to affect GABAergic neurotransmission. The aim of this study was to determine the influence of heat shock stress (HS) on GABAergic activity in C. elegans. For this purpose, we tested the effect of exposure to picrotoxin (PTX), gamma-aminobutyric acid (GABA), hydrogen peroxide, and HS on the occurrence of a shrinking response (SR) after nose touch stimulus in N2 (WT) worms. Moreover, the effect of HS on the expression of UNC-49 (GABAA receptor ortholog) in the EG1653 strain and the effect of GABA and PTX exposure on HSP-16.2 expression in the TJ375 strain were analyzed. PTX 1 mM- or H2O2 0.7 mM-exposed worms displayed a SR in about 80 % of trials. GABA exposure did not cause a SR. HS prompted the occurrence of a SR as did PTX 1 mM or H2O2 0.7 mM exposure. In addition, HS increased UNC-49 expression, and PTX augmented HSP-16.2 expression. Thus, the results of the present study suggest that oxidative stress, through either H2O2 exposure or application of heat shock, inactivates the GABAergic system, which subsequently would affect the oxidative stress response, perhaps by enhancing the activity of transcription factors DAF-16 and HSF-1, both regulated by the IIS pathway and related to hsp-16.2 expression.

  14. Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model

    Directory of Open Access Journals (Sweden)

    Virk Bhupinder

    2012-07-01

    Full Text Available Abstract Background Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits C. elegans lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging. Results Serendipitously, we isolated an E. coli mutant that slows C. elegans aging. We identified the disrupted gene to be aroD, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased C. elegans lifespan was caused by decreased availability of para-aminobenzoic acid, a precursor to folate. Consistent with this result, inhibition of folate synthesis by sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans lifespan. As expected, these treatments caused a decrease in bacterial and worm folate levels, as measured by mass spectrometry of intact folates. The folate cycle is essential for cellular biosynthesis. However, bacterial proliferation and C. elegans growth and reproduction were unaffected under the conditions that increased lifespan. Conclusions In this animal:microbe system, folates are in excess of that required for biosynthesis. This study suggests that microbial folate synthesis is a pharmacologically accessible target to slow animal aging without detrimental effects.

  15. Mesoscopic organization reveals the constraints governing Caenorhabditis elegans nervous system.

    Directory of Open Access Journals (Sweden)

    Raj Kumar Pan

    Full Text Available One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. The coordination of many different co-occurring processes at this level underlies the command and control of overall network activity. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations such as, optimizing for resource constraints (viz., total wiring cost and communication efficiency (i.e., network path length. Even including information about the genetic relatedness of the cells cannot account for the observed modular structure. Comparison with other complex networks designed for efficient transport (of signals or resources implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including

  16. Caenorhabditis elegans in regenerative medicine: a simple model for a complex discipline.

    Science.gov (United States)

    Aitlhadj, Layla; Stürzenbaum, Stephen R

    2014-06-01

    Stem cell research is a major focus of regenerative medicine, which amalgamates diverse disciplines ranging from developmental cell biology to chemical and genetic therapy. Although embryonic stem cells have provided the foundation of stem cell therapy, they offer an in vitro study system that might not provide the best insight into mechanisms and behaviour of cells within living organisms. Caenorhabditis elegans is a well defined model organism with highly conserved cell development and signalling processes that specify cell fate. Its genetic amenability coupled with its chemical screening applicability make the nematode well suited as an in vivo system in which regenerative therapy and stem cell processes can be explored. Here, we describe some of the major advances in stem cell research from the worm's perspective. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. The nematode Caenorhabditis elegans as a model of organophosphate-induced mammalian neurotoxicity

    International Nuclear Information System (INIS)

    Cole, Russell D.; Anderson, Gary L.; Williams, Phillip L.

    2004-01-01

    Fifteen organic phosphate pesticides were tested by computer tracking for their acute behavioral toxicity with the nematode Caenorhabditis elegans. Thirteen of these 15 chemicals are used as insecticides and are anticholesterase agents. The other two chemicals are used as herbicides. EC50 values for each chemical were compared to the corresponding LD50 acute lethality value in rats and mice. Order of toxicity was found to be significantly correlated in comparisons of C. elegans to both rats and mice. Mechanistic investigations were conducted by assaying 8 of the 15 chemicals for anticholinesterase activity in C. elegans. Significant cholinesterase inhibition was confirmed for five chemicals that had displayed high behavioral toxicity, while three chemicals of low behavioral toxicity showed no significant decrease in cholinesterase activity. Toxicity for two chemicals that do not inhibit cholinesterase in mammals was linked to pH effects. Detailed comparison of individual chemicals and metabolic issues are discussed. These results have positive implications for the use of C. elegans as a mammalian neurological model and support the use of C. elegans in early rounds of chemical toxicity screening

  18. Caenorhabditis elegans: A Useful Model for Studying Metabolic Disorders in Which Oxidative Stress Is a Contributing Factor

    Directory of Open Access Journals (Sweden)

    Elizabeth Moreno-Arriola

    2014-01-01

    Full Text Available Caenorhabditis elegans is a powerful model organism that is invaluable for experimental research because it can be used to recapitulate most human diseases at either the metabolic or genomic level in vivo. This organism contains many key components related to metabolic and oxidative stress networks that could conceivably allow us to increase and integrate information to understand the causes and mechanisms of complex diseases. Oxidative stress is an etiological factor that influences numerous human diseases, including diabetes. C. elegans displays remarkably similar molecular bases and cellular pathways to those of mammals. Defects in the insulin/insulin-like growth factor-1 signaling pathway or increased ROS levels induce the conserved phase II detoxification response via the SKN-1 pathway to fight against oxidative stress. However, it is noteworthy that, aside from the detrimental effects of ROS, they have been proposed as second messengers that trigger the mitohormetic response to attenuate the adverse effects of oxidative stress. Herein, we briefly describe the importance of C. elegans as an experimental model system for studying metabolic disorders related to oxidative stress and the molecular mechanisms that underlie their pathophysiology.

  19. Application of a mathematical model to describe the effects of chlorpyrifos on Caenorhabditis elegans development.

    Directory of Open Access Journals (Sweden)

    Windy A Boyd

    2009-09-01

    Full Text Available The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF and extinction (EXT of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing.L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0-75 microM and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT and log(TOF growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF and log(EXT, growth rates, and time to reach change points showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration.Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos affects C. elegans development in a concentration dependent

  20. Modeling the thermotaxis behavior of C.elegans based on the artificial neural network.

    Science.gov (United States)

    Li, Mingxu; Deng, Xin; Wang, Jin; Chen, Qiaosong; Tang, Yun

    2016-07-03

    ASBTRACT This research aims at modeling the thermotaxis behavior of C.elegans which is a kind of nematode with full clarified neuronal connections. Firstly, this work establishes the motion model which can perform the undulatory locomotion with turning behavior. Secondly, the thermotaxis behavior is modeled by nonlinear functions and the nonlinear functions are learned by artificial neural network. Once the artificial neural networks have been well trained, they can perform the desired thermotaxis behavior. Last, several testing simulations are carried out to verify the effectiveness of the model for thermotaxis behavior. This work also analyzes the different performances of the model under different environments. The testing results reveal the essence of the thermotaxis of C.elegans to some extent, and theoretically support the research on the navigation of the crawling robots.

  1. Reproductive fitness and dietary choice behavior of the genetic model organism Caenorhabditis elegans under semi-natural conditions.

    Science.gov (United States)

    Freyth, Katharina; Janowitz, Tim; Nunes, Frank; Voss, Melanie; Heinick, Alexander; Bertaux, Joanne; Scheu, Stefan; Paul, Rüdiger J

    2010-10-01

    Laboratory breeding conditions of the model organism C. elegans do not correspond with the conditions in its natural soil habitat. To assess the consequences of the differences in environmental conditions, the effects of air composition, medium and bacterial food on reproductive fitness and/or dietary-choice behavior of C. elegans were investigated. The reproductive fitness of C. elegans was maximal under oxygen deficiency and not influenced by a high fractional share of carbon dioxide. In media approximating natural soil structure, reproductive fitness was much lower than in standard laboratory media. In seminatural media, the reproductive fitness of C. elegans was low with the standard laboratory food bacterium E. coli (γ-Proteobacteria), but significantly higher with C. arvensicola (Bacteroidetes) and B. tropica (β-Proteobacteria) as food. Dietary-choice experiments in semi-natural media revealed a low preference of C. elegans for E. coli but significantly higher preferences for C. arvensicola and B. tropica (among other bacteria). Dietary-choice experiments under quasi-natural conditions, which were feasible by fluorescence in situ hybridization (FISH) of bacteria, showed a high preference of C. elegans for Cytophaga-Flexibacter-Bacteroides, Firmicutes, and β-Proteobacteria, but a low preference for γ-Proteobacteria. The results show that data on C. elegans under standard laboratory conditions have to be carefully interpreted with respect to their biological significance.

  2. Characterization of hydroxyurea resistance in C. elegans

    DEFF Research Database (Denmark)

    Brejning, Jeanette

    The soil nematode Caenorhabditis elegans has become a prominent model organism for studying aging and many age-related diseases. We use C. elegans to study the relationship between cancer and aging. To prevent cancer, cells are equipped with surveillance systems that detect damage and stop cells...... from dividing. These surveillance systems are collectively called cellular checkpoints. We have found that inactivation of certain checkpoint proteins, including p53, also cause resistance to the chemotherapeutic drug hydroxyurea (HU) that stalls replication. We have found that in C. elegans, HU...... inhibits ribonucleotide reductase (RNR). RNR is involved in synthesis of deoxyribonucleotide (dNTP) precursors for DNA replication and repair. Previously we have shown that inactivation of some checkpoint proteins can increase stress resistance and lifespan of C. elegans1. Interestingly, several genes...

  3. Staphylococcus aureus virulence factors identified by using a high-throughput Caenorhabditis elegans-killing model.

    Science.gov (United States)

    Begun, Jakob; Sifri, Costi D; Goldman, Samuel; Calderwood, Stephen B; Ausubel, Frederick M

    2005-02-01

    Staphylococcus aureus is an important human pathogen that is also able to kill the model nematode Caenorhabditis elegans. We constructed a 2,950-member Tn917 transposon insertion library in S. aureus strain NCTC 8325. Twenty-one of these insertions exhibited attenuated C. elegans killing, and of these, 12 contained insertions in different genes or chromosomal locations. Ten of these 12 insertions showed attenuated killing phenotypes when transduced into two different S. aureus strains, and 5 of the 10 mutants correspond to genes that have not been previously identified in signature-tagged mutagenesis studies. These latter five mutants were tested in a murine renal abscess model, and one mutant harboring an insertion in nagD exhibited attenuated virulence. Interestingly, Tn917 was shown to have a very strong bias for insertions near the terminus of DNA replication.

  4. Model-independent phenotyping of C. elegans locomotion using scale-invariant feature transform.

    Directory of Open Access Journals (Sweden)

    Yelena Koren

    Full Text Available To uncover the genetic basis of behavioral traits in the model organism C. elegans, a common strategy is to study locomotion defects in mutants. Despite efforts to introduce (semi-automated phenotyping strategies, current methods overwhelmingly depend on worm-specific features that must be hand-crafted and as such are not generalizable for phenotyping motility in other animal models. Hence, there is an ongoing need for robust algorithms that can automatically analyze and classify motility phenotypes quantitatively. To this end, we have developed a fully-automated approach to characterize C. elegans' phenotypes that does not require the definition of nematode-specific features. Rather, we make use of the popular computer vision Scale-Invariant Feature Transform (SIFT from which we construct histograms of commonly-observed SIFT features to represent nematode motility. We first evaluated our method on a synthetic dataset simulating a range of nematode crawling gaits. Next, we evaluated our algorithm on two distinct datasets of crawling C. elegans with mutants affecting neuromuscular structure and function. Not only is our algorithm able to detect differences between strains, results capture similarities in locomotory phenotypes that lead to clustering that is consistent with expectations based on genetic relationships. Our proposed approach generalizes directly and should be applicable to other animal models. Such applicability holds promise for computational ethology as more groups collect high-resolution image data of animal behavior.

  5. Exploring the envelope. Systematic alteration in the sex-determination system of the nematode caenorhabditis elegans.

    OpenAIRE

    Hodgkin, Jonathan

    2002-01-01

    The natural sexes of the nematode Caenorhabditis elegans are the self-fertilizing hermaphrodite (XX) and the male (XO). The underlying genetic pathway controlling sexual phenotype has been extensively investigated. Mutations in key regulatory genes have been used to create a series of stable populations in which sex is determined not by X chromosome dosage, but in a variety of other ways, many of which mimic the diverse sex-determination systems found in different animal species. Most of thes...

  6. Caenorhabditis elegans DAF-2 as a Model for Human Insulin Receptoropathies

    Directory of Open Access Journals (Sweden)

    David A. Bulger

    2017-01-01

    Full Text Available Human exome sequencing has dramatically increased the rate of identification of disease-associated polymorphisms. However, examining the functional consequences of those variants has created an analytic bottleneck. Insulin-like signaling in Caenorhabditis elegans has long provided a model to assess consequences of human insulin signaling mutations, but this has not been evaluated in the context of current genetic tools. We have exploited strains derived from the Million Mutation Project (MMP and gene editing to explore further the evolutionary relationships and conservation between the human and C. elegans insulin receptors. Of 40 MMP alleles analyzed in the C. elegans insulin-like receptor gene DAF-2, 35 exhibited insulin-like signaling indistinguishable from wild-type animals, indicating tolerated mutations. Five MMP alleles proved to be novel dauer-enhancing mutations, including one new allele in the previously uncharacterized C-terminus of DAF-2. CRISPR-Cas9 genome editing was used to confirm the phenotypic consequence of six of these DAF-2 mutations and to replicate an allelic series of known human disease mutations in a highly conserved tyrosine kinase active site residue, demonstrating the utility of C. elegans for directly modeling human disease. Our results illustrate the challenges associated with prediction of the phenotypic consequences of amino acid substitutions, the value of assaying mutant isoform function in vivo, and how recently developed tools and resources afford the opportunity to expand our understanding even of highly conserved regulatory modules such as insulin signaling. This approach may prove generally useful for modeling phenotypic consequences of candidate human pathogenic mutations in conserved signaling and developmental pathways.

  7. Caenorhabditis elegans DAF-2 as a Model for Human Insulin Receptoropathies.

    Science.gov (United States)

    Bulger, David A; Fukushige, Tetsunari; Yun, Sijung; Semple, Robert K; Hanover, John A; Krause, Michael W

    2017-01-05

    Human exome sequencing has dramatically increased the rate of identification of disease-associated polymorphisms. However, examining the functional consequences of those variants has created an analytic bottleneck. Insulin-like signaling in Caenorhabditis elegans has long provided a model to assess consequences of human insulin signaling mutations, but this has not been evaluated in the context of current genetic tools. We have exploited strains derived from the Million Mutation Project (MMP) and gene editing to explore further the evolutionary relationships and conservation between the human and C. elegans insulin receptors. Of 40 MMP alleles analyzed in the C. elegans insulin-like receptor gene DAF-2, 35 exhibited insulin-like signaling indistinguishable from wild-type animals, indicating tolerated mutations. Five MMP alleles proved to be novel dauer-enhancing mutations, including one new allele in the previously uncharacterized C-terminus of DAF-2 CRISPR-Cas9 genome editing was used to confirm the phenotypic consequence of six of these DAF-2 mutations and to replicate an allelic series of known human disease mutations in a highly conserved tyrosine kinase active site residue, demonstrating the utility of C. elegans for directly modeling human disease. Our results illustrate the challenges associated with prediction of the phenotypic consequences of amino acid substitutions, the value of assaying mutant isoform function in vivo, and how recently developed tools and resources afford the opportunity to expand our understanding even of highly conserved regulatory modules such as insulin signaling. This approach may prove generally useful for modeling phenotypic consequences of candidate human pathogenic mutations in conserved signaling and developmental pathways. Copyright © 2017 Bulger et al.

  8. Prowashonupana barley dietary fibre reduces body fat and increases insulin sensitivity in Caenorhabditis elegans model

    Science.gov (United States)

    Gao, Chenfei; King, Michael L.; Fitzpatrick, Zachary L.; Wei, Wenqian; King, Jason F.; Wang, Mingming; Greenway, Frank L.; Finley, John W.; Burton, Jeffrey H.; Johnson, William D.; Keenan, Michael J.; Enright, Frederick M.; Martin, Roy J.; Zheng, Jolene

    2016-01-01

    Prowashonupana barley (PWB) is high in β-glucan with moderate content of resistant starch. PWB reduced intestinal fat deposition (IFD) in wild type Caenorhabditis elegans (C. elegans, N2), and in sir-2.1 or daf-16 null mutants, and sustained a surrogate marker of lifespan, pharyngeal pumping rate (PPR), in N2, sir-2.1, daf-16, or daf-16/daf-2 mutants. Hyperglycaemia (2% glucose) reversed or reduced the PWB effect on IFD in N2 or daf-16/daf-2 mutants with a sustained PPR. mRNA expression of cpt-1, cpt-2, ckr-1, and gcy-8 were dose-dependently reduced in N2 or daf-16 mutants, elevated in daf-16/daf-2 mutants with reduction in cpt-1, and unchanged in sir-2.1 mutants. mRNA expressions were increased by hyperglycaemia in N2 or daf-16/daf-2 mutants, while reduced in sir-2.1 or daf-16 mutants. The effects of PWB in the C. elegans model appeared to be primarily mediated via sir-2.1, daf-16, and daf-16/daf-2. These data suggest that PWB and β-glucans may benefit hyperglycaemia-impaired lipid metabolism. PMID:27721901

  9. Genetic Determinants Associated With in Vivo Survival of Burkholderia cenocepacia in the Caenorhabditis elegans Model

    KAUST Repository

    Wong, Yee-Chin

    2018-05-29

    A Burkholderia cenocepacia infection usually leads to reduced survival and fatal cepacia syndrome in cystic fibrosis patients. The identification of B. cenocepacia essential genes for in vivo survival is key to designing new anti-infectives therapies. We used the Transposon-Directed Insertion Sequencing (TraDIS) approach to identify genes required for B. cenocepacia survival in the model infection host, Caenorhabditis elegans. A B. cenocepacia J2315 transposon pool of ∼500,000 mutants was used to infect C. elegans. We identified 178 genes as crucial for B. cenocepacia survival in the infected nematode. The majority of these genes code for proteins of unknown function, many of which are encoded by the genomic island BcenGI13, while other gene products are involved in nutrient acquisition, general stress responses and LPS O-antigen biosynthesis. Deletion of the glycosyltransferase gene wbxB and a histone-like nucleoid structuring (H-NS) protein-encoding gene (BCAL0154) reduced bacterial accumulation and attenuated virulence in C. elegans. Further analysis using quantitative RT-PCR indicated that BCAL0154 modulates B. cenocepacia pathogenesis via transcriptional regulation of motility-associated genes including fliC, fliG, flhD, and cheB1. This screen has successfully identified genes required for B. cenocepacia survival within the host-associated environment, many of which are potential targets for developing new antimicrobials.

  10. Genetic Determinants Associated With in Vivo Survival of Burkholderia cenocepacia in the Caenorhabditis elegans Model

    KAUST Repository

    Wong, Yee-Chin; Abd El Ghany, Moataz; Ghazzali, Raeece N. M.; Yap, Soon-Joo; Hoh, Chee-Choong; Pain, Arnab; Nathan, Sheila

    2018-01-01

    A Burkholderia cenocepacia infection usually leads to reduced survival and fatal cepacia syndrome in cystic fibrosis patients. The identification of B. cenocepacia essential genes for in vivo survival is key to designing new anti-infectives therapies. We used the Transposon-Directed Insertion Sequencing (TraDIS) approach to identify genes required for B. cenocepacia survival in the model infection host, Caenorhabditis elegans. A B. cenocepacia J2315 transposon pool of ∼500,000 mutants was used to infect C. elegans. We identified 178 genes as crucial for B. cenocepacia survival in the infected nematode. The majority of these genes code for proteins of unknown function, many of which are encoded by the genomic island BcenGI13, while other gene products are involved in nutrient acquisition, general stress responses and LPS O-antigen biosynthesis. Deletion of the glycosyltransferase gene wbxB and a histone-like nucleoid structuring (H-NS) protein-encoding gene (BCAL0154) reduced bacterial accumulation and attenuated virulence in C. elegans. Further analysis using quantitative RT-PCR indicated that BCAL0154 modulates B. cenocepacia pathogenesis via transcriptional regulation of motility-associated genes including fliC, fliG, flhD, and cheB1. This screen has successfully identified genes required for B. cenocepacia survival within the host-associated environment, many of which are potential targets for developing new antimicrobials.

  11. Chemotaxis of C. elegans in 3D media: a model for navigation of undulatory microswimmers

    Science.gov (United States)

    Patel, Amar; Bilbao, Alejandro; Rahman, Mizanur; Vanapalli, Siva; Blawzdziewicz, Jerzy

    2017-11-01

    While the natural environment of C. elegans consists of complex 3D media (e.g., decomposing organic matter and water), most studies of chemotactic behavior of this nematode are limited to 2D. We present a 3D chemotaxis model that combines a realistic geometrical representation of body movements associated with 3D maneuvers, an analysis of mechanical interactions of the nematode body with the surrounding medium to determine nematode trajectories, and a simple memory-function description of chemosensory apparatus that controls the frequency, magnitude, and timing of turning maneuvers. We show that two main chemotaxis strategies of C. elegans moving in 2D, i.e., the biased random walk and gradual turn, are effective also in 3D, provided that 2D turns are supplemented by the roll maneuvers that enable 3D reorientation. Optimal choices of chemosensing and gait-control parameters are discussed; we show that the nematode can maintain efficient chemotaxis in burrowing and swimming by adjusting the undulation frequency alone, without changing the chemotactic component of the body control. Understanding how C. elegans efficiently navigates in 3D media may help in developing self-navigating artificial microswimmers. Supported by NSF Grant No. CBET 1603627.

  12. NGT-3D: a simple nematode cultivation system to study Caenorhabditis elegans biology in 3D

    Directory of Open Access Journals (Sweden)

    Tong Young Lee

    2016-04-01

    Full Text Available The nematode Caenorhabditis elegans is one of the premier experimental model organisms today. In the laboratory, they display characteristic development, fertility, and behaviors in a two dimensional habitat. In nature, however, C. elegans is found in three dimensional environments such as rotting fruit. To investigate the biology of C. elegans in a 3D controlled environment we designed a nematode cultivation habitat which we term the nematode growth tube or NGT-3D. NGT-3D allows for the growth of both nematodes and the bacteria they consume. Worms show comparable rates of growth, reproduction and lifespan when bacterial colonies in the 3D matrix are abundant. However, when bacteria are sparse, growth and brood size fail to reach levels observed in standard 2D plates. Using NGT-3D we observe drastic deficits in fertility in a sensory mutant in 3D compared to 2D, and this defect was likely due to an inability to locate bacteria. Overall, NGT-3D will sharpen our understanding of nematode biology and allow scientists to investigate questions of nematode ecology and evolutionary fitness in the laboratory.

  13. lin-12 Notch functions in the adult nervous system of C. elegans

    Directory of Open Access Journals (Sweden)

    Tucey Tim M

    2005-07-01

    Full Text Available Abstract Background Notch signaling pathways are conserved across species and traditionally have been implicated in cell fate determination during embryonic development. Notch signaling components are also expressed postdevelopmentally in the brains of adult mice and Drosophila. Recent studies suggest that Notch signaling may play a role in the physiological, rather than developmental, regulation of neurons. Here, we investigate a new non-developmental role for Caenorhabditis elegans lin-12 Notch signaling in neurons regulating the spontaneous reversal rate during locomotion. Results The spontaneous reversal rate of C. elegans during normal locomotion is constant. Both lin-12 gain and loss of function mutant animals had significantly increased reversal rates compared to wild type controls. These defects were caused by lin-12 activity, because the loss of function defect could be rescued by a wild type lin-12 transgene. Furthermore, overexpression of lin-12 recapitulated the gain-of-function defect. Increasing or decreasing lin-12 activity in the postdevelopmental adult animal was sufficient to rapidly and reversibly increase reversals, thereby excluding a developmental role for lin-12. Although lin-12 is expressed in the vulval and somatic gonad lineages, we find that these tissues play no role in regulating reversal rates. In contrast, altering lin-12 activity specifically in the nervous system was sufficient to increase reversals. These behavioral changes require components of the canonical lin-12 signaling cascade, including the ligand lag-2 and the transcriptional effector lag-1. Finally, the C. elegans AMPA/kainate glutamate receptor homolog glr-1 shows strong genetic interactions with lin-12, suggesting that glr-1 and/or other glutamate gated channels may be targets of lin-12 regulation. Conclusion Our results demonstrate a neuronal role for lin-12 Notch in C. elegans and suggest that lin-12 acutely regulates neuronal physiology to

  14. Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency.

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    Jie Li

    Full Text Available The classical form of α1-antitrypsin deficiency (ATD is associated with hepatic fibrosis and hepatocellular carcinoma. It is caused by the proteotoxic effect of a mutant secretory protein that aberrantly accumulates in the endoplasmic reticulum of liver cells. Recently we developed a model of this deficiency in C. elegans and adapted it for high-content drug screening using an automated, image-based array scanning. Screening of the Library of Pharmacologically Active Compounds identified fluphenazine (Flu among several other compounds as a drug which reduced intracellular accumulation of mutant α1-antitrypsin Z (ATZ. Because it is representative of the phenothiazine drug class that appears to have autophagy enhancer properties in addition to mood stabilizing activity, and can be relatively easily re-purposed, we further investigated its effects on mutant ATZ. The results indicate that Flu reverses the phenotypic effects of ATZ accumulation in the C. elegans model of ATD at doses which increase the number of autophagosomes in vivo. Furthermore, in nanomolar concentrations, Flu enhances the rate of intracellular degradation of ATZ and reduces the cellular ATZ load in mammalian cell line models. In the PiZ mouse model Flu reduces the accumulation of ATZ in the liver and mediates a decrease in hepatic fibrosis. These results show that Flu can reduce the proteotoxicity of ATZ accumulation in vivo and, because it has been used safely in humans, this drug can be moved rapidly into trials for liver disease due to ATD. The results also provide further validation for drug discovery using C. elegans models that can be adapted to high-content drug screening platforms and used together with mammalian cell line and animal models.

  15. A Caenorhabditis elegans Host Model Correlates with Invasive Disease Caused by Staphylococcus aureus Recovered during an Outbreak in Neonatal Intensive Care

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    Kaiyu Wu

    2012-01-01

    Full Text Available BACKGROUND: Caenorhabditis elegans has previously been used as a host model to determine the virulence of clinical methicillin-resistant Staphylococcus aureus isolates. In the present study, methicillin-susceptible S aureus (MSSA strains associated with an outbreak in a neonatal intensive care unit (NICU were investigated using the C elegans model.

  16. An image-free opto-mechanical system for creating virtual environments and imaging neuronal activity in freely moving Caenorhabditis elegans.

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    Serge Faumont

    Full Text Available Non-invasive recording in untethered animals is arguably the ultimate step in the analysis of neuronal function, but such recordings remain elusive. To address this problem, we devised a system that tracks neuron-sized fluorescent targets in real time. The system can be used to create virtual environments by optogenetic activation of sensory neurons, or to image activity in identified neurons at high magnification. By recording activity in neurons of freely moving C. elegans, we tested the long-standing hypothesis that forward and reverse locomotion are generated by distinct neuronal circuits. Surprisingly, we found motor neurons that are active during both types of locomotion, suggesting a new model of locomotion control in C. elegans. These results emphasize the importance of recording neuronal activity in freely moving animals and significantly expand the potential of imaging techniques by providing a mean to stabilize fluorescent targets.

  17. Simulation of C. elegans thermotactic behavior in a linear thermal gradient using a simple phenomenological motility model.

    Science.gov (United States)

    Matsuoka, Tomohiro; Gomi, Sohei; Shingai, Ryuzo

    2008-01-21

    The nematode Caenorhabditis elegans has been reported to exhibit thermotaxis, a sophisticated behavioral response to temperature. However, there appears to be some inconsistency among previous reports. The results of population-level thermotaxis investigations suggest that C. elegans can navigate to the region of its cultivation temperature from nearby regions of higher or lower temperature. However, individual C. elegans nematodes appear to show only cryophilic tendencies above their cultivation temperature. A Monte-Carlo style simulation using a simple individual model of C. elegans provides insight into clarifying apparent inconsistencies among previous findings. The simulation using the thermotaxis model that includes the cryophilic tendencies, isothermal tracking and thermal adaptation was conducted. As a result of the random walk property of locomotion of C. elegans, only cryophilic tendencies above the cultivation temperature result in population-level thermophilic tendencies. Isothermal tracking, a period of active pursuit of an isotherm around regions of temperature near prior cultivation temperature, can strengthen the tendencies of these worms to gather around near-cultivation-temperature regions. A statistical index, the thermotaxis (TTX) L-skewness, was introduced and was useful in analyzing the population-level thermotaxis of model worms.

  18. View of environmental radiation effects from the study of radiation biology in C. elegans

    International Nuclear Information System (INIS)

    Sakashita, Tetsuya

    2011-01-01

    Caenorhabditis (C.) elegans is a non-parasitic soil nematode and is well-known as a unique model organism, because of its complete cell-lineage, nervous network and genome sequences. Also, C. elegans can be easily manipulated in the laboratory. These advantages make C. elegans as a good in vivo model system in the field of radiation biology. Radiation effects in C. elegans have been studied for three decades. Here, I briefly review the current knowledge of the biological effects of ionizing irradiation in C. elegans with a scope of environmental radiation effects. Firstly, basic information of C. elegans as a model organism is described. Secondly, historical view is reported on the study of radiation biology in C. elegans. Thirdly, our research on learning behavior is presented. Finally, an opinion of the use of C. elegans for environmental radiation protection is referred. I believe that C. elegans may be a good promising in vivo model system in the field of environmental radiation biology. (author)

  19. Virulence variations in Shigella and enteroinvasive Escherichia coli using the Caenorhabditis elegans model.

    Science.gov (United States)

    Fung, Crystal Ching; Octavia, Sophie; Mooney, Anne-Marie; Lan, Ruiting

    2015-01-01

    Shigella species and enteroinvasive Escherichia coli (EIEC) belong to the same species genetically, with remarkable phenotypic and genomic similarities. Shigella is the main cause of bacillary dysentery with around 160 million annual cases, while EIEC generally induces a milder disease compared to Shigella. This study aimed to determine virulence variations between Shigella and EIEC using the nematode Caenorhabditis elegans as a model host. Caenorhabditis elegans killing- and bacterial colonization assays were performed to examine the potential difference in virulence between Shigella and EIEC strains. Statistically significant difference in the survival rates of nematodes was demonstrated, with Shigella causing death at 88.24 ± 1.20% and EIEC at 94.37 ± 0.70%. The intestinal load of bacteria in the nematodes was found to be 7.65 × 10(4) ± 8.83 × 10(3) and 2.92 × 10(4) ± 6.26 × 10(3) CFU ml(-1) per nematode for Shigella and EIEC, respectively. Shigella dysenteriae serotype 1 which carries the Shiga toxin showed the lowest nematode survival rate at 82.6 ± 3.97% and highest bacterial colonization of 1.75 × 10(5) ± 8.17 × 10(4) CFU ml(-1), whereas a virulence plasmid-negative Shigella strain demonstrated 100 ± 0% nematode survival and lowest bacterial accumulation of 1.02 × 10(4) ± 7.23 × 10(2) CFU ml(-1). This study demonstrates C. elegans as an effective model for examining and comparing Shigella and EIEC virulence variation. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Development of everlasting flowers (Comanthera elegans (Bong. L.R. Parra & Giul. in three cultivation systems

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    Fernanda da Conceição Moreira

    2017-06-01

    Full Text Available Marketing the inflorescences of Comanthera elegans (Bong. L.R. Parra & Giul. represents a source of income to many families from extractives communities in the portion of the Espinhaço Range located in the state of Minas Gerais, Brazil. Cultivating this species stands out by allying income generation with conservation since the species is currently endangered. This study aimed to assess aspects of the development of C. elegans in three cultivation systems: beds, rows, and whole area. Sowing took place in January 2009 and the inflorescences were harvested in May 2010, which characterized the experimental period. Emergence; plant density; rates of flowering, mortality, resprouting, and recruiting of new individuals; and production of inflorescences per plant and per area were assessed. Emergence began approximately 50 days after sowing. Plant density ranged from 130 to 350 plants.m-2 among the three cultivation systems. The highest mortality rate (18% was observed at the peak of the dry season (August and the overall mortality rate over one reproductive cycle was 49%. Of the plants that lost the aerial part, 36% resprouted. Sprouting and seed germination accounted for 30 and 3% of the recruiting of new individuals, respectively. C. elegans had two bloom (AprilMay 2009 and April-May 2010: 5.4% of the plants bloomed in the first season and 78%, in the second. Each plant produced between three and 178 inflorescences and the highest inflorescence production in terms of weight (232 g.m-2 and number (2,910 inflorescences.m-2 was observed in the cultivation in beds at 1,624 kg.ha-1.

  1. The nematode Caenorhabditis elegans survives subfreezing temperatures in an isochoric system

    Energy Technology Data Exchange (ETDEWEB)

    Mikus, Hannah; Miller, Alexander [Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA 94720 (United States); Nastase, Gabriel, E-mail: traznasa@gmail.com [Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA 94720 (United States); Department of Building Services, Transilvania University of Brasov, Brasov, 500036 (Romania); Serban, Alexandru [Department of Building Services, Transilvania University of Brasov, Brasov, 500036 (Romania); Shapira, Michael [Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720 (United States); Rubinsky, Boris, E-mail: rubinsky@berkeley.edu [Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA 94720 (United States)

    2016-08-26

    This study is the first experimental evidence showing that a living multicellular organism, the nematode Caenorhabditis elegans, can survive subfreezing temperatures in an isochoric (constant volume) thermodynamic system, while immersed in a simple isotonic solution, without the addition of cryoprotectants. Some of the test conditions were more extreme than those found at the ice/water interface of the Antarctic subglacial Vostok lake. On earth, life takes place in an isobaric (constant pressure) environment. In isobaric systems, subfreezing temperature survival of organisms in nature and subfreezing temperature preservation of living material for biotechnology and medicine, is made possible by use of cryoprotective chemicals additives. Our theoretical thermodynamic studies suggested that in an isochoric system, living biological material could survive subfreezing temperatures, without any cryoprotective chemicals. By confirming the theoretical predictions, this paper suggests a new technology for subfreezing preservation of cells, organs and organisms of possible value for biotechnology and medicine as well as new possible mechanisms of living organism survival in nature. - Highlights: • Preservation of biological materials at, subfreezing temperatures, in an isochoric system, is demonstrated. • Experiments were performed with Caenorhabditis elegans to pressures of 65 MPa and temperatures of −6 °C. • Isochoric subfreezing temperature is a new preservation method that does not require the use of cryoprotectants.

  2. The nematode Caenorhabditis elegans survives subfreezing temperatures in an isochoric system

    International Nuclear Information System (INIS)

    Mikus, Hannah; Miller, Alexander; Nastase, Gabriel; Serban, Alexandru; Shapira, Michael; Rubinsky, Boris

    2016-01-01

    This study is the first experimental evidence showing that a living multicellular organism, the nematode Caenorhabditis elegans, can survive subfreezing temperatures in an isochoric (constant volume) thermodynamic system, while immersed in a simple isotonic solution, without the addition of cryoprotectants. Some of the test conditions were more extreme than those found at the ice/water interface of the Antarctic subglacial Vostok lake. On earth, life takes place in an isobaric (constant pressure) environment. In isobaric systems, subfreezing temperature survival of organisms in nature and subfreezing temperature preservation of living material for biotechnology and medicine, is made possible by use of cryoprotective chemicals additives. Our theoretical thermodynamic studies suggested that in an isochoric system, living biological material could survive subfreezing temperatures, without any cryoprotective chemicals. By confirming the theoretical predictions, this paper suggests a new technology for subfreezing preservation of cells, organs and organisms of possible value for biotechnology and medicine as well as new possible mechanisms of living organism survival in nature. - Highlights: • Preservation of biological materials at, subfreezing temperatures, in an isochoric system, is demonstrated. • Experiments were performed with Caenorhabditis elegans to pressures of 65 MPa and temperatures of −6 °C. • Isochoric subfreezing temperature is a new preservation method that does not require the use of cryoprotectants.

  3. Connecting a connectome to behavior: an ensemble of neuroanatomical models of C. elegans klinotaxis.

    Directory of Open Access Journals (Sweden)

    Eduardo J Izquierdo

    Full Text Available Increased efforts in the assembly and analysis of connectome data are providing new insights into the principles underlying the connectivity of neural circuits. However, despite these considerable advances in connectomics, neuroanatomical data must be integrated with neurophysiological and behavioral data in order to obtain a complete picture of neural function. Due to its nearly complete wiring diagram and large behavioral repertoire, the nematode worm Caenorhaditis elegans is an ideal organism in which to explore in detail this link between neural connectivity and behavior. In this paper, we develop a neuroanatomically-grounded model of salt klinotaxis, a form of chemotaxis in which changes in orientation are directed towards the source through gradual continual adjustments. We identify a minimal klinotaxis circuit by systematically searching the C. elegans connectome for pathways linking chemosensory neurons to neck motor neurons, and prune the resulting network based on both experimental considerations and several simplifying assumptions. We then use an evolutionary algorithm to find possible values for the unknown electrophsyiological parameters in the network such that the behavioral performance of the entire model is optimized to match that of the animal. Multiple runs of the evolutionary algorithm produce an ensemble of such models. We analyze in some detail the mechanisms by which one of the best evolved circuits operates and characterize the similarities and differences between this mechanism and other solutions in the ensemble. Finally, we propose a series of experiments to determine which of these alternatives the worm may be using.

  4. A microfluidic device with multi-valves system to enable several simultaneous exposure tests on Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Jung, Jaehoon; Masaru, Takeuchi; Nakajima, Masahiro; Huang, Qiang; Fukuda, Toshio

    2014-01-01

    In this paper, we report on a microfluidic device with a multi-valve system to conduct several exposure tests on Caenorhabditis elegans (C. elegans) simultaneously. It has pneumatic valves and no-moving-parts (NMP) valves. An NMP valve is incorporated with a chamber and enables the unidirectional movement of C. elegans in the chamber; once worms are loaded into the chamber, they cannot exit, regardless of the flow direction. To demonstrate the ability of the NMP valve to handle worms, we made a microfluidic device with three chambers. Each chamber was used to expose worms to Cd and Cu solutions, and K-medium. A pair of electrodes was installed in the device and the capacitance in-between the electrode was measured. When a C. elegans passed through the electrodes, the capacitance was changed. The capacitance change was proportional to the body volume of the worm, thus the body volume change by the heavy metal exposure was measured in the device. Thirty worms were divided into three groups and exposed to each solution. We confirmed that the different solutions induced differences in the capacitance changes for each group. These results indicate that our device is a viable method for simultaneously analyzing the effect of multiple stimuli on C. elegans. (paper)

  5. Proteomic investigation of Vibrio alginolyticus challenged Caenorhabditis elegans revealed regulation of cellular homeostasis proteins and their role in supporting innate immune system.

    Science.gov (United States)

    Durai, Sellegounder; Singh, Nirpendra; Kundu, Suman; Balamurugan, Krishnaswamy

    2014-08-01

    Caenorhabditis elegans has been the preferred model system for many investigators to study pathogenesis. In the present investigation, regulation of C. elegans proteome was explored against V. alginolyticus infection using quantitative proteomics approach. Proteins were separated using 2D-DIGE and the differentially regulated proteins were identified using PMF and MALDI TOF/TOF analysis. The results thus obtained were validated using Western blotting for candidate proteins. The corresponding transcriptional regulation was quantified subsequently using real-time PCR. Interaction network for candidate proteins was predicted using search tool for the retrieval of interacting genes/proteins (STRING) and functional validation was performed using respective mutant strains. Out of the 25 proteins identified, 21 proteins appeared to be upregulated while four were downregulated. Upregulated proteins included those involved in stress-response (PDI-2, HSP-6), immune-response (protein kinase -18, GST-8) and energy-production (ATP-2) while proteins involved in structural maintenance (IFB-2) and lipid metabolism (SODH-1) were downregulated. The roles of these players in the host system during Vibrio infection was analyzed in vivo using wild type and mutant C. elegans. Survival assays using mutants lacking pdi-2, ire-1, and xbp-1 displayed enhanced susceptibility to V. alginolyticus. Cellular stress generated by V. alginolyticus was determined using ROS assay. This is the first report of proteome changes in C. elegans against V. alginolyticus challenge and highlights the significance of unfolded protein response (UPR) pathway during bacterial infection. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. A new Caenorhabditis elegans model of human huntingtin 513 aggregation and toxicity in body wall muscles.

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    Amy L Lee

    Full Text Available Expanded polyglutamine repeats in different proteins are the known determinants of at least nine progressive neurodegenerative disorders whose symptoms include cognitive and motor impairment that worsen as patients age. One such disorder is Huntington's Disease (HD that is caused by a polyglutamine expansion in the human huntingtin protein (htt. The polyglutamine expansion destabilizes htt leading to protein misfolding, which in turn triggers neurodegeneration and the disruption of energy metabolism in muscle cells. However, the molecular mechanisms that underlie htt proteotoxicity have been somewhat elusive, and the muscle phenotypes have not been well studied. To generate tools to elucidate the basis for muscle dysfunction, we engineered Caenorhabditis elegans to express a disease-associated 513 amino acid fragment of human htt in body wall muscle cells. We show that this htt fragment aggregates in C. elegans in a polyglutamine length-dependent manner and is toxic. Toxicity manifests as motor impairment and a shortened lifespan. Compared to previous models, the data suggest that the protein context in which a polyglutamine tract is embedded alters aggregation propensity and toxicity, likely by affecting interactions with the muscle cell environment.

  7. In vivo visualization and quantification of mitochondrial morphology in C. elegans

    NARCIS (Netherlands)

    Smith, R.L.; De Vos, W.H.; de Boer, R.; Manders, E.M.M.; van der Spek, H.; Weissig, V.; Edeas, M.

    2015-01-01

    Caenorhabditis elegans is a highly malleable model system, intensively used for functional, genetic, cytometric, and integrative studies. Due to its simplicity and large muscle cell number, C. elegans has frequently been used to study mitochondrial deficiencies caused by disease or drug toxicity.

  8. A cellular and regulatory map of the cholinergic nervous system of C. elegans

    Science.gov (United States)

    Pereira, Laura; Kratsios, Paschalis; Serrano-Saiz, Esther; Sheftel, Hila; Mayo, Avi E; Hall, David H; White, John G; LeBoeuf, Brigitte; Garcia, L Rene; Alon, Uri; Hobert, Oliver

    2015-01-01

    Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly. DOI: http://dx.doi.org/10.7554/eLife.12432.001 PMID:26705699

  9. Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Troemel, Emily R; Félix, Marie-Anne; Whiteman, Noah K; Barrière, Antoine; Ausubel, Frederick M

    2008-12-09

    For decades the soil nematode Caenorhabditis elegans has been an important model system for biology, but little is known about its natural ecology. Recently, C. elegans has become the focus of studies of innate immunity and several pathogens have been shown to cause lethal intestinal infections in C. elegans. However none of these pathogens has been shown to invade nematode intestinal cells, and no pathogen has been isolated from wild-caught C. elegans. Here we describe an intracellular pathogen isolated from wild-caught C. elegans that we show is a new species of microsporidia. Microsporidia comprise a large class of eukaryotic intracellular parasites that are medically and agriculturally important, but poorly understood. We show that microsporidian infection of the C. elegans intestine proceeds through distinct stages and is transmitted horizontally. Disruption of a conserved cytoskeletal structure in the intestine called the terminal web correlates with the release of microsporidian spores from infected cells, and appears to be part of a novel mechanism by which intracellular pathogens exit from infected cells. Unlike in bacterial intestinal infections, the p38 MAPK and insulin/insulin-like growth factor (IGF) signaling pathways do not appear to play substantial roles in resistance to microsporidian infection in C. elegans. We found microsporidia in multiple wild-caught isolates of Caenorhabditis nematodes from diverse geographic locations. These results indicate that microsporidia are common parasites of C. elegans in the wild. In addition, the interaction between C. elegans and its natural microsporidian parasites provides a system in which to dissect intracellular intestinal infection in vivo and insight into the diversity of pathogenic mechanisms used by intracellular microbes.

  10. Pseudomonas aeruginosa PA14 pathogenesis in Caenorhabditis elegans.

    Science.gov (United States)

    Kirienko, Natalia V; Cezairliyan, Brent O; Ausubel, Frederick M; Powell, Jennifer R

    2014-01-01

    The nematode Caenorhabditis elegans is a simple model host for studying the interaction between bacterial pathogens such as Pseudomonas aeruginosa and the metazoan innate immune system. Powerful genetic and molecular tools in both C. elegans and P. aeruginosa facilitate the identification and analysis of bacterial virulence factors as well as host defense factors. Here we describe three different assays that use the C. elegans-P. aeruginosa strain PA14 host-pathogen system. Fast Killing is a toxin-mediated death that depends on a diffusible toxin produced by PA14 but not on live bacteria. Slow Killing is due to an active infection in which bacteria colonize the C. elegans intestinal lumen. Liquid Killing is designed for high-throughput screening of chemical libraries for anti-infective compounds. Each assay has unique features and, interestingly, the PA14 virulence factors involved in killing are different in each assay.

  11. Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits.

    Science.gov (United States)

    Watson, Emma; MacNeil, Lesley T; Ritter, Ashlyn D; Yilmaz, L Safak; Rosebrock, Adam P; Caudy, Amy A; Walhout, Albertha J M

    2014-02-13

    Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits

    Science.gov (United States)

    Watson, Emma; MacNeil, Lesley T.; Ritter, Ashlyn D.; Yilmaz, L. Safak; Rosebrock, Adam P.; Caudy, Amy A.; Walhout, Albertha J. M.

    2014-01-01

    SUMMARY Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here we used an interspecies systems biology approach with Caenorhabditis elegans and two if its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal’s gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development and reduces fertility, but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology. PMID:24529378

  13. Caenorhabditis elegans as a model for understanding ROS function in physiology and disease

    Directory of Open Access Journals (Sweden)

    Antonio Miranda-Vizuete

    2017-04-01

    Full Text Available ROS (reactive oxygen species are potentially damaging by-products of aerobic metabolism which, unchecked, can have detrimental effects on cell function. However, it is now widely accepted that, at physiological levels, certain ROS play important roles in cell signaling, acting as second messengers to regulate cell choices that contribute to the development, adaptation and survival of plants and animals. Despite important recent advances in the biochemical tools available to study redox-signaling, the molecular mechanisms underlying most of these responses remain poorly understood, particularly in multicellular organisms. As we will review here, C. elegans has emerged as a powerful animal model to elucidate these and other aspects of redox biology.

  14. Decrease of Staphylococcus aureus Virulence by Helcococcus kunzii in a Caenorhabditis elegans Model.

    Science.gov (United States)

    Ngba Essebe, Christelle; Visvikis, Orane; Fines-Guyon, Marguerite; Vergne, Anne; Cattoir, Vincent; Lecoustumier, Alain; Lemichez, Emmanuel; Sotto, Albert; Lavigne, Jean-Philippe; Dunyach-Remy, Catherine

    2017-01-01

    Social bacterial interactions are considered essential in numerous infectious diseases, particularly in wounds. Foot ulcers are a common complication in diabetic patients and these ulcers become frequently infected. This infection is usually polymicrobial promoting cell-to-cell communications. Staphylococcus aureus is the most prevalent pathogen isolated. Its association with Helcococcus kunzii , commensal Gram-positive cocci, is frequently described. The aim of this study was to assess the impact of co-infection on virulence of both H. kunzii and S. aureus strains in a Caenorhabditis elegans model. To study the host response, qRT-PCRs targeting host defense genes were performed. We observed that H. kunzii strains harbored a very low (LT50: 5.7 days ± 0.4) or an absence of virulence (LT50: 6.9 days ± 0.5). In contrast, S. aureus strains (LT50: 2.9 days ± 0.4) were significantly more virulent than all H. kunzii ( P aureus strains were associated, H. kunzii significantly reduced the virulence of the S. aureus strain in nematodes (LT50 between 4.4 and 5.2 days; P aureus led to a strong induction of defense genes ( lys-5, sodh-1 , and cyp-37B1 ) while H. kunzii did not. No statistical difference of host response genes expression was observed when C. elegans were infected with either S. aureus alone or with S. aureus + H. kunzii . Moreover, two well-characterized virulence factors ( hla and agr ) present in S. aureus were down-regulated when S. aureus were co-infected with H. kunzii . This study showed that H. kunzii decreased the virulence of S. aureus without modifying directly the host defense response. Factor(s) produced by this bacterium modulating the staphylococci virulence must be investigated.

  15. Congruence between distribution modelling and phylogeographical analyses reveals Quaternary survival of a toadflax species (Linaria elegans) in oceanic climate areas of a mountain ring range.

    Science.gov (United States)

    Fernández-Mazuecos, Mario; Vargas, Pablo

    2013-06-01

    · The role of Quaternary climatic shifts in shaping the distribution of Linaria elegans, an Iberian annual plant, was investigated using species distribution modelling and molecular phylogeographical analyses. Three hypotheses are proposed to explain the Quaternary history of its mountain ring range. · The distribution of L. elegans was modelled using the maximum entropy method and projected to the last interglacial and to the last glacial maximum (LGM) using two different paleoclimatic models: the Community Climate System Model (CCSM) and the Model for Interdisciplinary Research on Climate (MIROC). Two nuclear and three plastid DNA regions were sequenced for 24 populations (119 individuals sampled). Bayesian phylogenetic, phylogeographical, dating and coalescent-based population genetic analyses were conducted. · Molecular analyses indicated the existence of northern and southern glacial refugia and supported two routes of post-glacial recolonization. These results were consistent with the LGM distribution as inferred under the CCSM paleoclimatic model (but not under the MIROC model). Isolation between two major refugia was dated back to the Riss or Mindel glaciations, > 100 kyr before present (bp). · The Atlantic distribution of inferred refugia suggests that the oceanic (buffered)-continental (harsh) gradient may have played a key and previously unrecognized role in determining Quaternary distribution shifts of Mediterranean plants. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  16. Genetic Mechanisms of Coffee Extract Protection in a Caenorhabditis elegans Model of β-Amyloid Peptide Toxicity

    OpenAIRE

    Dostal, Vishantie; Roberts, Christine M.; Link, Christopher D.

    2010-01-01

    Epidemiological studies have reported that coffee and/or caffeine consumption may reduce Alzheimer's disease (AD) risk. We found that coffee extracts can similarly protect against β-amyloid peptide (Aβ) toxicity in a transgenic Caenorhabditis elegans Alzheimer's disease model. The primary protective component(s) in this model is not caffeine, although caffeine by itself can show moderate protection. Coffee exposure did not decrease Aβ transgene expression and did not need to be present during...

  17. Lactobacillus casei stimulates phase-II detoxification system and rescues malathion-induced physiological impairments in Caenorhabditis elegans.

    Science.gov (United States)

    Kamaladevi, Arumugam; Ganguli, Abhijit; Balamurugan, Krishnaswamy

    2016-01-01

    Malathion, an organophosphorus insecticide, is renowned for its inhibitory action on acetylcholinesterase (AChE) enzyme that eventually leads to widespread disturbance in the normal physiological and behavioral activities of any organism. Lactic acid bacteria (LAB) are still an underexploited and inexhaustible source of significant pharmaceutical thrust. In the present study, Caenorhabditis elegans was employed to identify and characterize the indigenous LAB isolated from different traditional food against malathion-induced toxicity. The results demonstrated that malathion at its LD50 concentration decreased various C. elegans physiological parameters such as survival, feeding, and locomotion. Among the screened isolates, L. casei exhibited an excellent protective efficacy against malathion-induced toxicity by increasing the level of AChE and thereby rescued all physiological parameters of C. elegans. In addition, short-term exposure and food choice assay divulged that L. casei could serve as a better food to protect C. elegans from noxious environment. The expression analysis unveiled that L. casei gavage upregulated the phase-II detoxification enzymes coding genes metallothioneins (mtl-1 and mtl-2) and glutathione-S-transferase (gst-8) and thereby eliminated malathion from the host system. Furthermore, the upregulation of ace-3 along with down-regulation of cyp35a in the nematodes supplemented with L. casei could be attributed to attenuate the malathion-induced physiological defects in C. elegans. Thus, the present study reports that an indigenous LAB-L. casei could serve as a promising protective agent against the harmful effects of pesticide. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The Si elegans project at the interface of experimental and computational Caenorhabditis elegans neurobiology and behavior

    Science.gov (United States)

    Petrushin, Alexey; Ferrara, Lorenzo; Blau, Axel

    2016-12-01

    Objective. In light of recent progress in mapping neural function to behavior, we briefly and selectively review past and present endeavors to reveal and reconstruct nervous system function in Caenorhabditis elegans through simulation. Approach. Rather than presenting an all-encompassing review on the mathematical modeling of C. elegans, this contribution collects snapshots of pathfinding key works and emerging technologies that recent single- and multi-center simulation initiatives are building on. We thereby point out a few general limitations and problems that these undertakings are faced with and discuss how these may be addressed and overcome. Main results. Lessons learned from past and current computational approaches to deciphering and reconstructing information flow in the C. elegans nervous system corroborate the need of refining neural response models and linking them to intra- and extra-environmental interactions to better reflect and understand the actual biological, biochemical and biophysical events that lead to behavior. Together with single-center research efforts, the Si elegans and OpenWorm projects aim at providing the required, in some cases complementary tools for different hardware architectures to support advancement into this direction. Significance. Despite its seeming simplicity, the nervous system of the hermaphroditic nematode C. elegans with just 302 neurons gives rise to a rich behavioral repertoire. Besides controlling vital functions (feeding, defecation, reproduction), it encodes different stimuli-induced as well as autonomous locomotion modalities (crawling, swimming and jumping). For this dichotomy between system simplicity and behavioral complexity, C. elegans has challenged neurobiologists and computational scientists alike. Understanding the underlying mechanisms that lead to a context-modulated functionality of individual neurons would not only advance our knowledge on nervous system function and its failure in pathological

  19. Elucidating the Role of CaMKK in Cell Cycle and Cell Fate using a C. elegans model

    Science.gov (United States)

    2000-07-01

    domain) or the Aspergillus homologue, anCaMKB (48% overall)(Figure 2). To functionally compare the C. elegans proteins with their mammalian homologues...subunit on the yeast proteome . EMBO J 18, 4157-68 (1999). 14 19. H. Tokumitsu et aL, Substrate recognition by Ca2+/Calmodulin-dependent protein kinase...2 Nicholas School of the Environment Duke University, Durham, NC 27710 Ethan@Duke.Edu In a variety of models, from Xenopus oocytes to Aspergillus to

  20. On-Demand Isolation and Manipulation of C. elegans by In Vitro Maskless Photopatterning.

    Directory of Open Access Journals (Sweden)

    C Ryan Oliver

    Full Text Available Caenorhabditis elegans (C. elegans is a model organism for understanding aging and studying animal behavior. Microfluidic assay techniques have brought widespread advances in C. elegans research; however, traditional microfluidic assays such as those based on soft lithography require time-consuming design and fabrication cycles and offer limited flexibility in changing the geometric environment during experimentation. We present a technique for maskless photopatterning of a biocompatible hydrogel on an NGM (Agar substrate, enabling dynamic manipulation of the C. elegans culture environment in vitro. Maskless photopatterning is performed using a projector-based microscope system largely built from off-the-shelf components. We demonstrate the capabilities of this technique by building micropillar arrays during C. elegans observation, by fabricating free-floating mechanisms that can be actuated by C. elegans motion, by using freehand drawing to isolate individual C. elegans in real time, and by patterning arrays of mazes for isolation and fitness testing of C. elegans populations. In vitro photopatterning enables rapid and flexible design of experiment geometry as well as real-time interaction between the researcher and the assay such as by sequential isolation of individual organisms. Future adoption of image analysis and machine learning techniques could be used to acquire large datasets and automatically adapt the assay geometry.

  1. Biotransformation of fluorophenyl pyridine carboxylic acids by the model fungus Cunninghamella elegans.

    Science.gov (United States)

    Palmer-Brown, William; Dunne, Brian; Ortin, Yannick; Fox, Mark A; Sandford, Graham; Murphy, Cormac D

    2017-09-01

    1. Fluorine plays a key role in the design of new drugs and recent FDA approvals included two fluorinated drugs, tedizolid phosphate and vorapaxar, both of which contain the fluorophenyl pyridyl moiety. 2. To investigate the likely phase-I (oxidative) metabolic fate of this group, various fluorinated phenyl pyridine carboxylic acids were incubated with the fungus Cunninghamella elegans, which is an established model of mammalian drug metabolism. 3.  19 F NMR spectroscopy established the degree of biotransformation, which varied depending on the position of fluorine substitution, and gas chromatography-mass spectrometry (GC-MS) identified alcohols and hydroxylated carboxylic acids as metabolites. The hydroxylated metabolites were further structurally characterised by nuclear magnetic resonance spectroscopy (NMR), which demonstrated that hydroxylation occurred on the 4' position; fluorine in that position blocked the hydroxylation. 4. The fluorophenyl pyridine carboxylic acids were not biotransformed by rat liver microsomes and this was a consequence of inhibitory action, and thus, the fungal model was crucial in obtaining metabolites to establish the mechanism of catabolism.

  2. Biological response to radiation. Studies of model organism, C. elegans, with micro-ion beam

    International Nuclear Information System (INIS)

    Higashitani, Atsushi

    2006-01-01

    Described are mainly author's studies on radiation response and its biological significance in a nematode, C. elegans, particularly focusing its germ cells. The model organism is bisexual and the mature one is suitable to observe the development, differentiation and concomitant chromosome dynamics of male and female germ cells, and accordingly, the responses occurring in those cells at different stages post irradiation of the whole worm. Authors have shown in the organism irradiated by 100 Gy X-ray that pachytene cells in meiosis have high radio-resistance due to their increased expression of enzymes related with homologous recombination. They have also presented the apoptotic cascade in germ cells triggered by radiation by comparison of wild type and ab1-1-gene-deleted worms. Micro-beam of 12 C 5+ ion in Takasaki Ion Accelerators for Advanced Radiation Application (TIARA) has been used to irradiate the body parts of the worm to study the bystander effects, which has revealed that germ cells are shielded from the effect in the worm. It is thought important to use the micro-beam, with which the irradiation area can be precisely controllable, for studying the bystander effect in a body of higher animals like a mouse as well as in worm somatic cells. (T.I.)

  3. Virulence of Klebsiella pneumoniae isolates harboring bla KPC-2 carbapenemase gene in a Caenorhabditis elegans model.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Lavigne

    Full Text Available Klebsiella pneumoniae carbapenemase (KPC is a carbapenemase increasingly reported worldwide in Enterobacteriaceae. The aim of this study was to analyze the virulence of several KPC-2-producing K. pneumoniae isolates. The studied strains were (i five KPC-2 clinical strains from different geographical origins, belonging to different ST-types and possessing plasmids of different incompatibility groups; (ii seven transformants obtained after electroporation of either these natural KPC plasmids or a recombinant plasmid harboring only the bla KPC-2 gene into reference strains K. pneumoniae ATCC10031/CIP53153; and (iii five clinical strains cured of plasmids. The virulence of K. pneumoniae isolates was evaluated in the Caenorhabditis elegans model. The clinical KPC producers and transformants were significantly less virulent (LT50: 5.5 days than K. pneumoniae reference strain (LT50: 4.3 days (p<0.01. However, the worldwide spread KPC-2 positive K. pneumoniae ST258 strains and reference strains containing plasmids extracted from K. pneumoniae ST258 strains had a higher virulence than KPC-2 strains belonging to other ST types (LT50: 5 days vs. 6 days, p<0.01. The increased virulence observed in cured strains confirmed this trend. The bla KPC-2 gene itself was not associated to increased virulence.

  4. C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging.

    Directory of Open Access Journals (Sweden)

    Tjakko J van Ham

    2008-03-01

    Full Text Available Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a C. elegans model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha- synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders.

  5. BIOINFORMATICS MODEL OF THE CARAPACE SCUTE PATTERN OF THE RED-EARED SLIDER TRACHEMYS SCRIPTA ELEGANS (WIED-NEUWIED, 1839

    Directory of Open Access Journals (Sweden)

    Andrey Kiladze

    2017-10-01

    Full Text Available The scutes located on the carapace of the red-eared slider Trachemys scripta elegans (Wied-Neuwied, 1839 have been modeled. Bioinformatics modeling of carapace’s scutes were carried out by utilizing the Voronoi decomposition and Delaunay triangulation method. These two geometric techniques allow the patterns of vertebral and costal scutes to be recreated. The proposed model may have a certain value for taxonomy as well as for estimating the symmetry of the morphological structures, which is important for the purposes of biomimetics.

  6. High-throughput screening for novel anti-infectives using a C. elegans pathogenesis model.

    Science.gov (United States)

    Conery, Annie L; Larkins-Ford, Jonah; Ausubel, Frederick M; Kirienko, Natalia V

    2014-03-14

    In recent history, the nematode Caenorhabditis elegans has provided a compelling platform for the discovery of novel antimicrobial drugs. In this protocol, we present an automated, high-throughput C. elegans pathogenesis assay, which can be used to screen for anti-infective compounds that prevent nematodes from dying due to Pseudomonas aeruginosa. New antibiotics identified from such screens would be promising candidates for treatment of human infections, and also can be used as probe compounds to identify novel targets in microbial pathogenesis or host immunity. Copyright © 2014 John Wiley & Sons, Inc.

  7. Track-a-worm, an open-source system for quantitative assessment of C. elegans locomotory and bending behavior.

    Directory of Open Access Journals (Sweden)

    Sijie Jason Wang

    Full Text Available A major challenge of neuroscience is to understand the circuit and gene bases of behavior. C. elegans is commonly used as a model system to investigate how various gene products function at specific tissue, cellular, and synaptic foci to produce complicated locomotory and bending behavior. The investigation generally requires quantitative behavioral analyses using an automated single-worm tracker, which constantly records and analyzes the position and body shape of a freely moving worm at a high magnification. Many single-worm trackers have been developed to meet lab-specific needs, but none has been widely implemented for various reasons, such as hardware difficult to assemble, and software lacking sufficient functionality, having closed source code, or using a programming language that is not broadly accessible. The lack of a versatile system convenient for wide implementation makes data comparisons difficult and compels other labs to develop new worm trackers. Here we describe Track-A-Worm, a system rich in functionality, open in source code, and easy to use. The system includes plug-and-play hardware (a stereomicroscope, a digital camera and a motorized stage, custom software written to run with Matlab in Windows 7, and a detailed user manual. Grayscale images are automatically converted to binary images followed by head identification and placement of 13 markers along a deduced spline. The software can extract and quantify a variety of parameters, including distance traveled, average speed, distance/time/speed of forward and backward locomotion, frequency and amplitude of dominant bends, overall bending activities measured as root mean square, and sum of all bends. It also plots worm travel path, bend trace, and bend frequency spectrum. All functionality is performed through graphical user interfaces and data is exported to clearly-annotated and documented Excel files. These features make Track-A-Worm a good candidate for implementation in

  8. The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans during bacterial infection, by modulating the nematode's innate immune response

    DEFF Research Database (Denmark)

    Jakobsen, Henrik; Bojer, Martin Saxtorph; Marinus, Martin G.

    2013-01-01

    pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This indicates that Harmane has a complex effect on the innate immune system of C. elegans. Harmane could therefore be a useful tool in the further research into C. elegans immunity....... Since the innate immunity of C. elegans has a high degree of evolutionary conservation, drugs such as Harmane could also be possible alternatives to classic antibiotics. The C. elegans model could prove to be useful for selection and development of such drugs.......The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin...

  9. Cell fate determination in the Caenorhabditis elegans epidermal lineages

    NARCIS (Netherlands)

    Soete, G.A.J.

    2007-01-01

    The starting point for this work was to use the hypodermal seam of C. elegans as a model system to study cell fate determination. Even though the seam is a relatively simple developmental system, the mechanisms that control cell fate determination in the seam lineages are connected in a highly

  10. Caenorhabditis elegans: nature and nurture gift to nematode parasitologists.

    Science.gov (United States)

    Salinas, Gustavo; Risi, Gastón

    2017-12-06

    The free-living nematode Caenorhabditis elegans is the simplest animal model organism to work with. Substantial knowledge and tools have accumulated over 50 years of C. elegans research. The use of C. elegans relating to parasitic nematodes from a basic biology standpoint or an applied perspective has increased in recent years. The wealth of information gained on the model organism, the use of the powerful approaches and technologies that have advanced C. elegans research to parasitic nematodes and the enormous success of the omics fields have contributed to bridge the divide between C. elegans and parasite nematode researchers. We review key fields, such as genomics, drug discovery and genetics, where C. elegans and nematode parasite research have convened. We advocate the use of C. elegans as a model to study helminth metabolism, a neglected area ready to advance. How emerging technologies being used in C. elegans can pave the way for parasitic nematode research is discussed.

  11. In vivo screening platform for shiga toxin-producing Escherichia coli (STEC using Caenorhabditis elegans as a model.

    Directory of Open Access Journals (Sweden)

    Su-Bin Hwang

    Full Text Available Shiga toxin-producing Escherichia coli (STEC strains are the main cause of bacillary dysentery, although STEC strains generally induce milder disease symptoms compared to Shigella species. This study aimed to determine the virulence of STEC using the nematode Caenorhabditis elegans as a model host. Worm killing, fertility and bacterial colonisation assays were performed to examine the potential difference in the virulence of STEC strains compared to that of the control E. coli OP50 strains on which worms were fed. A statistically significant difference in the survival rates of C. elegans was observed in that the STEC strains caused death in 8-10 days and the E. coli OP50 strains caused death in 15 days. STEC strains severely reduced the fertility of the worms. The intestinal load of bacteria in the adult stage nematodes harbouring the E. coli OP50 strains was found to be 3.5 log CFU mL-1. In contrast, the STEC strains E15, E18 and E22 harboured 4.1, 4.2 and 4.7 log CFU ml-1 per nematode, respectively. The heat-killed STEC strains significantly increased the longevity of the worms compared to the non-heated STEC strains. In addition, PCR-based genomic profiling of shiga toxin genes, viz., stx1 and stx2, identified in selected STEC strains revealed that these toxins may be associated with the virulence of the STEC strains. This study demonstrated that C. elegans is an effective model to examine and compare the pathogenicity and virulence variation of STEC strains to that of E. coli OP50 strains.

  12. Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency.

    Directory of Open Access Journals (Sweden)

    Erin E Cummings

    Full Text Available α1-antitrypsin deficiency (ATD predisposes patients to both loss-of-function (emphysema and gain-of-function (liver cirrhosis phenotypes depending on the type of mutation. Although the Z mutation (ATZ is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (<20% normal plasma levels or null (<1% normal levels alleles. The deficient alleles, like ATZ, misfold in the ER where they accumulate as toxic monomers, oligomers and aggregates. Thus, deficient alleles may predispose to both gain- and loss-of-function phenotypes. Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype induced by the aggregation-prone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS, showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gain-of-function proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of

  13. Genome wide analyses of metal responsive genes in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Michael eAschner

    2012-04-01

    Full Text Available Metals are major contaminants that influence human health. Many metals have physiologic roles, but excessive levels can be harmful. Advances in technology have made toxicogenomic analyses possible to characterize the effects of metal exposure on the entire genome. Much of what is known about cellular responses to metals has come from mammalian systems; however the use of non-mammalian species is gaining wider attention. Caenorhabditis elegans (C. elegans is a small round worm whose genome has been fully sequenced and its development from egg to adult is well characterized. It is an attractive model for high throughput screens due to its short lifespan, ease of genetic mutability, low cost and high homology with humans. Research performed in C. elegans has led to insights in apoptosis, gene expression and neurodegeneration, all of which can be altered by metal exposure. Additionally, by using worms one can potentially study how the mechanisms that underline differential responses to metals in nematodes and humans, allowing for identification of novel pathways and therapeutic targets. In this review, toxicogenomic studies performed in C. elegans exposed to various metals will be discussed, highlighting how this non-mammalian system can be utilized to study cellular processes and pathways induced by metals. Recent work focusing on neurodegeneration in Parkinson’s disease will be discussed as an example of the usefulness of genetic screens in C. elegans and the novel findings that can be produced.

  14. Behavioral response and cell morphology changes of caenorhabditis elegans under high power millimeter wave irradiation

    International Nuclear Information System (INIS)

    Ren Changhong; Gao Yan; Wu Yonghong; Xu Zhiwei; Zhang Chenggang; Yuan Guangjiang; Xu Shouxi; Su Yinong; Liu Pukun

    2010-01-01

    C. elegans were exposed to high power millimeter waves (MMWs) with different mean power densities, to investigate their behavioral response and cell morphology changes under MMW irradiation. The time-course photomicrography system was used to record the behavioral changes of C. elegans. The behavioral response and cell morphology changes were further observed by stereoscopic microscopes. The results show that freely moving C. elegans will escape from the MMW irradiation region quickly. After the exposure to MMWs with output mean power of 10 W and 12 W, the bending speed of C. elegans increases significantly at first, while the movement gradually slows down until the bodies get rigid. However, exposed to 5 W MMW, C. elegans show a distinctive tolerant reaction because of the thermal effect. In addition, cell morphological observations show that the nuclear structure of the eggs are abnormal after abnormal after MMW irradiation. High power MMW significantly affects the behaviors and cell morphology of C. elegans, which suggests the C. elegans could be used as a typical model species to study the biological effects of MMW irradiation. (authors)

  15. Insect-derived cecropins display activity against Acinetobacter baumannii in a whole-animal high-throughput Caenorhabditis elegans model.

    Science.gov (United States)

    Jayamani, Elamparithi; Rajamuthiah, Rajmohan; Larkins-Ford, Jonah; Fuchs, Beth Burgwyn; Conery, Annie L; Vilcinskas, Andreas; Ausubel, Frederick M; Mylonakis, Eleftherios

    2015-03-01

    The rise of multidrug-resistant Acinetobacter baumannii and a concomitant decrease in antibiotic treatment options warrants a search for new classes of antibacterial agents. We have found that A. baumannii is pathogenic and lethal to the model host organism Caenorhabditis elegans and have exploited this phenomenon to develop an automated, high-throughput, high-content screening assay in liquid culture that can be used to identify novel antibiotics effective against A. baumannii. The screening assay involves coincubating C. elegans with A. baumannii in 384-well plates containing potential antibacterial compounds. At the end of the incubation period, worms are stained with a dye that stains only dead animals, and images are acquired using automated microscopy and then analyzed using an automated image analysis program. This robust assay yields a Z' factor consistently greater than 0.7. In a pilot experiment to test the efficacy of the assay, we screened a small custom library of synthetic antimicrobial peptides (AMPs) that were synthesized using publicly available sequence data and/or transcriptomic data from immune-challenged insects. We identified cecropin A and 14 other cecropin or cecropin-like peptides that were able to enhance C. elegans survival in the presence of A. baumannii. Interestingly, one particular hit, BR003-cecropin A, a cationic peptide synthesized by the mosquito Aedes aegypti, showed antibiotic activity against a panel of Gram-negative bacteria and exhibited a low MIC (5 μg/ml) against A. baumannii. BR003-cecropin A causes membrane permeability in A. baumannii, which could be the underlying mechanism of its lethality. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Maple Syrup Decreases TDP-43 Proteotoxicity in a Caenorhabditis elegans Model of Amyotrophic Lateral Sclerosis (ALS).

    Science.gov (United States)

    Aaron, Catherine; Beaudry, Gabrielle; Parker, J Alex; Therrien, Martine

    2016-05-04

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing death of the motor neurons. Proteotoxicity caused by TDP-43 protein is an important aspect of ALS pathogenesis, with TDP-43 being the main constituent of the aggregates found in patients. We have previously tested the effect of different sugars on the proteotoxicity caused by the expression of mutant TDP-43 in Caenorhabditis elegans. Here we tested maple syrup, a natural compound containing many active molecules including sugars and phenols, for neuroprotective activity. Maple syrup decreased several age-dependent phenotypes caused by the expression of TDP-43(A315T) in C. elegans motor neurons and requires the FOXO transcription factor DAF-16 to be effective.

  17. Untwisting the Caenorhabditis elegans embryo

    Science.gov (United States)

    Christensen, Ryan Patrick; Bokinsky, Alexandra; Santella, Anthony; Wu, Yicong; Marquina-Solis, Javier; Guo, Min; Kovacevic, Ismar; Kumar, Abhishek; Winter, Peter W; Tashakkori, Nicole; McCreedy, Evan; Liu, Huafeng; McAuliffe, Matthew; Mohler, William; Colón-Ramos, Daniel A; Bao, Zhirong; Shroff, Hari

    2015-01-01

    The nematode Caenorhabditis elegans possesses a simple embryonic nervous system with few enough neurons that the growth of each cell could be followed to provide a systems-level view of development. However, studies of single cell development have largely been conducted in fixed or pre-twitching live embryos, because of technical difficulties associated with embryo movement in late embryogenesis. We present open-source untwisting and annotation software (http://mipav.cit.nih.gov/plugin_jws/mipav_worm_plugin.php) that allows the investigation of neurodevelopmental events in late embryogenesis and apply it to track the 3D positions of seam cell nuclei, neurons, and neurites in multiple elongating embryos. We also provide a tutorial describing how to use the software (Supplementary file 1) and a detailed description of the untwisting algorithm (Appendix). The detailed positional information we obtained enabled us to develop a composite model showing movement of these cells and neurites in an 'average' worm embryo. The untwisting and cell tracking capabilities of our method provide a foundation on which to catalog C. elegans neurodevelopment, allowing interrogation of developmental events in previously inaccessible periods of embryogenesis. DOI: http://dx.doi.org/10.7554/eLife.10070.001 PMID:26633880

  18. Untwisting the Caenorhabditis elegans embryo.

    Science.gov (United States)

    Christensen, Ryan Patrick; Bokinsky, Alexandra; Santella, Anthony; Wu, Yicong; Marquina-Solis, Javier; Guo, Min; Kovacevic, Ismar; Kumar, Abhishek; Winter, Peter W; Tashakkori, Nicole; McCreedy, Evan; Liu, Huafeng; McAuliffe, Matthew; Mohler, William; Colón-Ramos, Daniel A; Bao, Zhirong; Shroff, Hari

    2015-12-03

    The nematode Caenorhabditis elegans possesses a simple embryonic nervous system with few enough neurons that the growth of each cell could be followed to provide a systems-level view of development. However, studies of single cell development have largely been conducted in fixed or pre-twitching live embryos, because of technical difficulties associated with embryo movement in late embryogenesis. We present open-source untwisting and annotation software (http://mipav.cit.nih.gov/plugin_jws/mipav_worm_plugin.php) that allows the investigation of neurodevelopmental events in late embryogenesis and apply it to track the 3D positions of seam cell nuclei, neurons, and neurites in multiple elongating embryos. We also provide a tutorial describing how to use the software (Supplementary file 1) and a detailed description of the untwisting algorithm (Appendix). The detailed positional information we obtained enabled us to develop a composite model showing movement of these cells and neurites in an 'average' worm embryo. The untwisting and cell tracking capabilities of our method provide a foundation on which to catalog C. elegans neurodevelopment, allowing interrogation of developmental events in previously inaccessible periods of embryogenesis.

  19. Use of C. Elegans as a model organism for sensing the effects of ELF-EMFs

    Energy Technology Data Exchange (ETDEWEB)

    Lacchini, A H; Everington, M L; Augousti, A T; Walker, A J [School of Life Sciences, Kingston University London (United Kingdom)

    2007-07-15

    For the past two decades, there have been concerns and controversy about the effects on human health of the increased exposure to extremely-low-frequency (ELF) electromagnetic fields (EMFs) resulting from electrification, in both residential and industrial settings. Several epidemiological studies have implicated ELF-EMFs averaging 0.4 {mu}mUTesla (T) or more in increased risk of cancer, especially childhood leukaemia [1,2]; there have also been many reports demonstrating effects of power-frequency EMFs on cells [outlined in 1,3]. Unfortunately, however, the precise mechanisms by which ELF-EMFs exert biological effects have proven difficult to define and results of various studies have often been hard to reproduce [1]. We believe that C. elegans offers an exciting opportunity to elucidate the effects of power-frequency EMFs on cell signalling pathways within the whole organism and are therefore investigating the effects of ELF-EMF exposure on MAPK signalling in intact worms and fertilized embryos. Through taking a targeted approach to studying the effects of ELF-EMF's on MAPK signalling in C. elegans we aim to gather data that is physiologically relevant. Presently, this research is at a preliminary stage of preparation, and more detailed results on the exposure of Caenorhabditis elegans to ELF-EMF radiation will be presented at the conference itself.

  20. Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.

    Science.gov (United States)

    Apfeld, Javier; Fontana, Walter

    2017-12-23

    It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson's disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson's disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson's disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans . Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.

  1. Life-History Traits of the Model Organism Pristionchus pacificus Recorded Using the Hanging Drop Method: Comparison with Caenorhabditis elegans.

    Science.gov (United States)

    Gilarte, Patricia; Kreuzinger-Janik, Bianca; Majdi, Nabil; Traunspurger, Walter

    2015-01-01

    The nematode Pristionchus pacificus is of growing interest as a model organism in evolutionary biology. However, despite multiple studies of its genetics, developmental cues, and ecology, the basic life-history traits (LHTs) of P. pacificus remain unknown. In this study, we used the hanging drop method to follow P. pacificus at the individual level and thereby quantify its LHTs. This approach allowed direct comparisons with the LHTs of Caenorhabditis elegans recently determined using this method. When provided with 5×10(9) Escherichia coli cells ml(-1) at 20°C, the intrinsic rate of natural increase of P. pacificus was 1.125 (individually, per day); mean net production was 115 juveniles produced during the life-time of each individual, and each nematode laid an average of 270 eggs (both fertile and unfertile). The mean age of P. pacificus individuals at first reproduction was 65 h, and the average life span was 22 days. The life cycle of P. pacificus is therefore slightly longer than that of C. elegans, with a longer average life span and hatching time and the production of fewer progeny.

  2. Life-History Traits of the Model Organism Pristionchus pacificus Recorded Using the Hanging Drop Method: Comparison with Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Patricia Gilarte

    Full Text Available The nematode Pristionchus pacificus is of growing interest as a model organism in evolutionary biology. However, despite multiple studies of its genetics, developmental cues, and ecology, the basic life-history traits (LHTs of P. pacificus remain unknown. In this study, we used the hanging drop method to follow P. pacificus at the individual level and thereby quantify its LHTs. This approach allowed direct comparisons with the LHTs of Caenorhabditis elegans recently determined using this method. When provided with 5×10(9 Escherichia coli cells ml(-1 at 20°C, the intrinsic rate of natural increase of P. pacificus was 1.125 (individually, per day; mean net production was 115 juveniles produced during the life-time of each individual, and each nematode laid an average of 270 eggs (both fertile and unfertile. The mean age of P. pacificus individuals at first reproduction was 65 h, and the average life span was 22 days. The life cycle of P. pacificus is therefore slightly longer than that of C. elegans, with a longer average life span and hatching time and the production of fewer progeny.

  3. Royal jelly promotes DAF-16-mediated proteostasis to tolerate β-amyloid toxicity in C. elegans model of Alzheimer's disease.

    Science.gov (United States)

    Wang, Xiaoxia; Cao, Min; Dong, Yuqing

    2016-08-23

    Numerous studies have demonstrated that dietary intervention may promote health and help prevent Alzheimer's disease (AD). We recently reported that bee products of royal jelly (RJ) and enzyme-treated royal jelly (eRJ) were potent to promote healthy aging in C. elegans. Here, we examined whether RJ/eRJ consumption may benefit to mitigate the AD symptom in the disease model of C. elegans. Our results showed that RJ/eRJ supplementation significantly delayed the body paralysis in AD worms, suggesting the β-amyloid (Aβ) toxicity attenuation effects of RJ/eRJ. Genetic analyses suggested that RJ/eRJ-mediated alleviation of Aβ toxicity in AD worms required DAF-16, rather than HSF-1 and SKN-1, in an insulin/IGF signaling dependent manner. Moreover, RJ/eRJ modulated the transactivity of DAF-16 and dramatically improved the protein solubility in aged worms. Given protein solubility is a hallmark of healthy proteostasis, our findings demonstrated that RJ/eRJ supplementation improved proteostasis, and this promotion depended on the transactivity of DAF-16. Collectively, the present study not only elucidated the possible anti-AD mechanism of RJ/eRJ, but also provided evidence from a practical point of view to shed light on the extensive correlation of proteostasis and the prevention of neurodegenerative disorders.

  4. Mechanistic modeling analysis of micro-evolutive responses from a Caenorhabditis elegans population exposed to a radioactive metallic stress

    International Nuclear Information System (INIS)

    Goussen, Benoit

    2013-01-01

    The evolution of toxic effects at a relevant scale is an important challenge for the ecosystem protection. Indeed, pollutants may impact populations over long-term and represent a new evolutionary force which can be adding itself to the natural selection forces. Thereby, it is necessary to acquire knowledge on the phenotypics and genetics changes that may appear in populations submitted to stress over several generations. Usually statistical analyses are performed to analyse such multi-generational studies. The use of a mechanistic mathematical model may provide a way to fully understand the impact of pollutants on the populations' dynamics. Such kind of model allows the integration of biological and toxic processes into the analysis of eco-toxicological data and the assessment of interactions between these processes. The aim of this Ph.D. project was to assess the contributions of the mechanistic modelling to the analysis of evolutionary experiment assessing long-term exposure. To do so, a three step strategy has been developed. Foremost, a multi-generational study was performed to assess the evolution of two populations of the ubiquitous nematode Caenorhabditis elegans in control conditions or exposed to 1.1 mM of uranium. Several generations were selected to assess growth, reproduction, and dose-responses relationships, through exposure to a range of concentrations (from 0 to 1.2 mM U) with all endpoints measured daily. A first statistical analysis was then performed. In a second step, a bio-energetic model adapted to the assessment of eco-toxicological data (DEBtox) was developed on C. elegans. Its numerical behaviour was analysed. Finally, this model was applied to all the selected generations in order to infer parameters values for the two populations and to assess their evolutions. Results highlighted an impact of the uranium starting from 0.4 mM U on both C. elegans' growth and reproduction. Results from the mechanistic analysis indicate this effect is due

  5. A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Arjumand Ghazi

    2009-09-01

    Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is influenced by the germline. When germline-stem cells are removed, aging slows and lifespan is increased. The mechanism by which somatic tissues respond to loss of the germline is not well-understood. Surprisingly, we have found that a predicted transcription elongation factor, TCER-1, plays a key role in this process. TCER-1 is required for loss of the germ cells to increase C. elegans' lifespan, and it acts as a regulatory switch in the pathway. When the germ cells are removed, the levels of TCER-1 rise in somatic tissues. This increase is sufficient to trigger key downstream events, as overexpression of tcer-1 extends the lifespan of normal animals that have an intact reproductive system. Our findings suggest that TCER-1 extends lifespan by promoting the expression of a set of genes regulated by the conserved, life-extending transcription factor DAF-16/FOXO. Interestingly, TCER-1 is not required for DAF-16/FOXO to extend lifespan in animals with reduced insulin/IGF-1 signaling. Thus, TCER-1 specifically links the activity of a broadly deployed transcription factor, DAF-16/FOXO, to longevity signals from reproductive tissues.

  6. HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans.

    Science.gov (United States)

    Kinet, Maxime J; Malin, Jennifer A; Abraham, Mary C; Blum, Elyse S; Silverman, Melanie R; Lu, Yun; Shaham, Shai

    2016-03-08

    Apoptosis is a prominent metazoan cell death form. Yet, mutations in apoptosis regulators cause only minor defects in vertebrate development, suggesting that another developmental cell death mechanism exists. While some non-apoptotic programs have been molecularly characterized, none appear to control developmental cell culling. Linker-cell-type death (LCD) is a morphologically conserved non-apoptotic cell death process operating in Caenorhabditis elegans and vertebrate development, and is therefore a compelling candidate process complementing apoptosis. However, the details of LCD execution are not known. Here we delineate a molecular-genetic pathway governing LCD in C. elegans. Redundant activities of antagonistic Wnt signals, a temporal control pathway, and mitogen-activated protein kinase kinase signaling control heat shock factor 1 (HSF-1), a conserved stress-activated transcription factor. Rather than protecting cells, HSF-1 promotes their demise by activating components of the ubiquitin proteasome system, including the E2 ligase LET-70/UBE2D2 functioning with E3 components CUL-3, RBX-1, BTBD-2, and SIAH-1. Our studies uncover design similarities between LCD and developmental apoptosis, and provide testable predictions for analyzing LCD in vertebrates.

  7. The mevalonate pathway in C. Elegans

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    Rauthan Manish

    2011-12-01

    Full Text Available Abstract The mevalonate pathway in human is responsible for the synthesis of cholesterol and other important biomolecules such as coenzyme Q, dolichols and isoprenoids. These molecules are required in the cell for functions ranging from signaling to membrane integrity, protein prenylation and glycosylation, and energy homeostasis. The pathway consists of a main trunk followed by sub-branches that synthesize the different biomolecules. The majority of our knowledge about the mevalonate pathway is currently focused on the cholesterol synthesis branch, which is the target of the cholesterol-lowering statins; less is known about the function and regulation of the non-cholesterol-related branches. To study them, we need a biological system where it is possible to specifically modulate these metabolic branches individually or in groups. The nematode Caenorhabditis elegans (C. elegans is a promising model to study these non-cholesterol branches since its mevalonate pathway seems very well conserved with that in human except that it has no cholesterol synthesis branch. The simple genetic makeup and tractability of C. elegans makes it relatively easy to identify and manipulate key genetic components of the mevalonate pathway, and to evaluate the consequences of tampering with their activity. This general experimental approach should lead to new insights into the physiological roles of the non-cholesterol part of the mevalonate pathway. This review will focus on the current knowledge related to the mevalonate pathway in C. elegans and its possible applications as a model organism to study the non-cholesterol functions of this pathway.

  8. A model of the effect of uncertainty on the C elegans L2/L2d decision.

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    Leon Avery

    Full Text Available At the end of the first larval stage, the C elegans larva chooses between two developmental pathways, an L2 committed to reproductive development and an L2d, which has the option of undergoing reproductive development or entering the dauer diapause. I develop a quantitative model of this choice using mathematical tools developed for pricing financial options. The model predicts that the optimal decision must take into account not only the expected potential for reproductive growth, but also the uncertainty in that expected potential. Because the L2d has more flexibility than the L2, it is favored in unpredictable environments. I estimate that the ability to take uncertainty into account may increase reproductive value by as much as 5%, and discuss possible experimental tests for this ability.

  9. Multibiomarker responses in aquatic insect Belostoma elegans (Hemiptera) to organic pollution in freshwater system.

    Science.gov (United States)

    Lavarías, S; Ocon, C; van Oosterom, V López; Laino, A; Medesani, D A; Fassiano, A; Garda, H; Donadelli, J; de Molina, M Ríos; Capítulo, A Rodrigues

    2017-01-01

    The present study analyzes a battery of biomarkers in the water bug Belostoma elegans from a stream polluted with organic matter (OMS), and another one considered as reference site (RS) during spring-summer season (December to March). Biochemical parameters of glucidic, lipidic and oxidative metabolic pathways were analyzed in males and females of this insect. In general, no significant differences were observed in all biomarkers assayed between both sexes, except lactate concentration which was higher in males than in females (p insects collected in both streams (p insects from RS compared to those from OMS (p insects collected from both streams. Nevertheless, the significant increase observed in superoxide dismutase and catalase activities (p insects from RS compared to those from OMS with lower dissolved oxygen. Regarding those responding parameters, males accounted for the differences between the two sites during the study period. In conclusion, our results support that lipidic energetic reserves and antioxidant enzyme activities in B. elegans could be used as biomarkers of environmental pollution by organic matter.

  10. The Caenorhabditis elegans Q neuroblasts: A powerful system to study cell migration at single-cell resolution in vivo.

    Science.gov (United States)

    Rella, Lorenzo; Fernandes Póvoa, Euclides E; Korswagen, Hendrik C

    2016-04-01

    During development, cell migration plays a central role in the formation of tissues and organs. Understanding the molecular mechanisms that drive and control these migrations is a key challenge in developmental biology that will provide important insights into disease processes, including cancer cell metastasis. In this article, we discuss the Caenorhabditis elegans Q neuroblasts and their descendants as a tool to study cell migration at single-cell resolution in vivo. The highly stereotypical migration of these cells provides a powerful system to study the dynamic cytoskeletal processes that drive migration as well as the evolutionarily conserved signaling pathways (including different Wnt signaling cascades) that guide the cells along their specific trajectories. Here, we provide an overview of what is currently known about Q neuroblast migration and highlight the live-cell imaging, genome editing, and quantitative gene expression techniques that have been developed to study this process. © 2016 Wiley Periodicals, Inc.

  11. Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans.

    Science.gov (United States)

    Furuhashi, Tsubasa; Sakamoto, Kazuichi

    2016-03-25

    The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Tetraspanin is required for generation of reactive oxygen species by the dual oxidase system in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Hiroki Moribe

    2012-09-01

    Full Text Available Reactive oxygen species (ROS are toxic but essential molecules responsible for host defense and cellular signaling. Conserved NADPH oxidase (NOX family enzymes direct the regulated production of ROS. Hydrogen peroxide (H(2O(2 generated by dual oxidases (DUOXs, a member of the NOX family, is crucial for innate mucosal immunity. In addition, H(2O(2 is required for cellular signaling mediated by protein modifications, such as the thyroid hormone biosynthetic pathway in mammals. In contrast to other NOX isozymes, the regulatory mechanisms of DUOX activity are less understood. Using Caenorhabditis elegans as a model, we demonstrate that the tetraspanin protein is required for induction of the DUOX signaling pathway in conjunction with the dual oxidase maturation factor (DUOXA. In the current study, we show that genetic mutation of DUOX (bli-3, DUOXA (doxa-1, and peroxidase (mlt-7 in C. elegans causes the same defects as a tetraspanin tsp-15 mutant, represented by exoskeletal deficiencies due to the failure of tyrosine cross-linking of collagen. The deficiency in the tsp-15 mutant was restored by co-expression of bli-3 and doxa-1, indicating the involvement of tsp-15 in the generation of ROS. H(2O(2 generation by BLI-3 was completely dependent on TSP-15 when reconstituted in mammalian cells. We also demonstrated that TSP-15, BLI-3, and DOXA-1 form complexes in vitro and in vivo. Cell-fusion-based analysis suggested that association with TSP-15 at the cell surface is crucial for BLI-3 activation to release H(2O(2. This study provides the first evidence for an essential role of tetraspanin in ROS generation.

  13. Downregulation of the Hsp90 system causes defects in muscle cells of Caenorhabditis elegans.

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    Andreas M Gaiser

    Full Text Available The ATP-dependent molecular chaperone Hsp90 is required for the activation of a variety of client proteins involved in various cellular processes. Despite the abundance of known client proteins, functions of Hsp90 in the organismal context are not fully explored. In Caenorhabditis elegans, Hsp90 (DAF-21 has been implicated in the regulation of the stress-resistant dauer state, in chemosensing and in gonad formation. In a C. elegans strain carrying a DAF-21 mutation with a lower ATP turnover, we observed motility defects. Similarly, a reduction of DAF-21 levels in wild type nematodes leads to reduced motility and induction of the muscular stress response. Furthermore, aggregates of the myosin MYO-3 are visible in muscle cells, if DAF-21 is depleted, implying a role of Hsp90 in the maintenance of muscle cell functionality. Similar defects can also be observed upon knockdown of the Hsp90-cochaperone UNC-45. In life nematodes YFP-DAF-21 localizes to the I-band and the M-line of the muscular ultrastructure, but the protein is not stably attached there. The Hsp90-cofactor UNC-45-CFP contrarily can be found in all bands of the nematode muscle ultrastructure and stably associates with the UNC-54 containing A-band. Thus, despite the physical interaction between DAF-21 and UNC-45, apparently the two proteins are not always localized to the same muscular structures. While UNC-45 can stably bind to myofilaments in the muscular ultrastructure, Hsp90 (DAF-21 appears to participate in the maintenance of muscle structures as a transiently associated diffusible factor.

  14. Gustatory Behaviour in Caenorhabditis elegans

    NARCIS (Netherlands)

    R.K. Hukema (Renate)

    2006-01-01

    textabstractThe nematode C. elegans is an ideal model-organism to study the genetics of behaviour (Brenner, 1974). It is capable of sensing salts and we discriminate three different responses: it is attracted to low salt concentrations (Ward, 1973; Dusenbery et al., 1974), it avoids high salt

  15. Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage.

    Science.gov (United States)

    Charão, Mariele Feiffer; Souto, Caroline; Brucker, Natália; Barth, Anelise; Jornada, Denise S; Fagundez, Daiandra; Ávila, Daiana Silva; Eifler-Lima, Vera L; Guterres, Silvia S; Pohlmann, Adriana R; Garcia, Solange Cristina

    2015-01-01

    Caenorhabditis elegans is an alternative in vivo model that is being successfully used to assess the pharmacological and toxic effects of drugs. The exponential growth of nanotechnology requires the use of alternative in vivo models to assess the toxic effects of theses nanomaterials. The use of polymeric nanocapsules has shown promising results for drug delivery. Moreover, these formulations have not been used in cases of intoxication, such as in treatment of paraquat (PQ) poisoning. Thus, the use of drugs with properties improved by nanotechnology is a promising approach to overcome the toxic effects of PQ. This research aimed to evaluate the absorption of rhodamine B-labeled melatonin (Mel)-loaded lipid-core nanocapsules (LNC) by C. elegans, the application of this model in nanotoxicology, and the protection of Mel-LNC against PQ damage. The formulations were prepared by self-assembly and characterized by particle sizing, zeta potential, drug content, and encapsulation efficiency. The results demonstrated that the formulations had narrow size distributions. Rhodamine B-labeled Mel-LNC were orally absorbed and distributed in the worms. The toxicity assessment of LNC showed a lethal dose 50% near the highest dose tested, indicating low toxicity of the nanocapsules. Moreover, pretreatment with Mel-LNC significantly increased the survival rate, reduced the reactive oxygen species, and maintained the development in C. elegans exposed to PQ compared to those worms that were either untreated or pretreated with free Mel. These results demonstrated for the first time the uptake and distribution of Mel-LNC by a nematode, and indicate that while LNC is not toxic, Mel-LNC prevents the effects of PQ poisoning. Thus, C. elegans may be an interesting alternative model to test the nanocapsules toxicity and efficacy.

  16. Revelations from the Nematode Caenorhabditis elegans on the Complex Interplay of Metal Toxicological Mechanisms

    Directory of Open Access Journals (Sweden)

    Ebany J. Martinez-Finley

    2011-01-01

    Full Text Available Metals have been definitively linked to a number of disease states. Due to the widespread existence of metals in our environment from both natural and anthropogenic sources, understanding the mechanisms of their cellular detoxification is of upmost importance. Organisms have evolved cellular detoxification systems including glutathione, metallothioneins, pumps and transporters, and heat shock proteins to regulate intracellular metal levels. The model organism, Caenorhabditis elegans (C. elegans, contains these systems and provides several advantages for deciphering the mechanisms of metal detoxification. This review provides a brief summary of contemporary literature on the various mechanisms involved in the cellular detoxification of metals, specifically, antimony, arsenic, cadmium, copper, manganese, mercury, and depleted uranium using the C. elegans model system for investigation and analysis.

  17. Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans.

    Science.gov (United States)

    Blanchette, Cassandra R; Thackeray, Andrea; Perrat, Paola N; Hekimi, Siegfried; Bénard, Claire Y

    2017-01-01

    The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation. In humans, mutations in either of the exostosin genes EXT1 and EXT2 lead to osteosarcomas or multiple exostoses. Complete loss of any of the exostosin glycosyltransferases in mouse, fish, flies and worms leads to drastic morphogenetic defects and embryonic lethality. Here we identify and study previously unavailable viable hypomorphic mutations in the two C. elegans exostosin glycosyltransferases genes, rib-1 and rib-2. These partial loss-of-function mutations lead to a severe reduction of HS levels and result in profound but specific developmental defects, including abnormal cell and axonal migrations. We find that the expression pattern of the HS copolymerase is dynamic during embryonic and larval morphogenesis, and is sustained throughout life in specific cell types, consistent with HSPGs playing both developmental and post-developmental roles. Cell-type specific expression of the HS copolymerase shows that HS elongation is required in both the migrating neuron and neighboring cells to coordinate migration guidance. Our findings provide insights into general principles underlying HSPG function in development.

  18. Does trans-lesion synthesis explain the UV-radiation resistance of DNA synthesis in C.elegans embryos?

    International Nuclear Information System (INIS)

    Hartman, Phil; Reddy, Jennifer; Svendsen, Betty-Ann

    1991-01-01

    Over 10-fold larger fluences were required to inhibit both DNA synthesis and cell division in wild-type C.elegans embryos as compared with other model systems or C.elegans rad mutants. In addition, unlike in other organisms, the molecular weight of daughter DNA strands was reduced only after large, superlethal fluences. The molecular weight of nascent DNA fragments exceeded the interdimer distance by up to 19-fold, indicating that C.elegans embryos can replicate through non-instructional lesions. This putative trans-lesion synthetic capability may explain the refractory nature of UV-radiation on embryonic DNA synthesis and nuclear division in C.elegans. (author). 42 refs.; 7 figs

  19. Does trans-lesion synthesis explain the UV-radiation resistance of DNA synthesis in C. elegans embryos

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, Phil; Reddy, Jennifer; Svendsen, Betty-Ann [Texas Christian Univ., Fort Worth, TX (United States). Dept. of Biology

    1991-09-01

    Over 10-fold larger fluences were required to inhibit both DNA synthesis and cell division in wild-type C.elegans embryos as compared with other model systems or C.elegans rad mutants. In addition, unlike in other organisms, the molecular weight of daughter DNA strands was reduced only after large, superlethal fluences. The molecular weight of nascent DNA fragments exceeded the interdimer distance by up to 19-fold, indicating that C.elegans embryos can replicate through non-instructional lesions. This putative trans-lesion synthetic capability may explain the refractory nature of UV-radiation on embryonic DNA synthesis and nuclear division in C.elegans. (author). 42 refs.; 7 figs.

  20. Simulation-based model checking approach to cell fate specification during Caenorhabditis elegans vulval development by hybrid functional Petri net with extension

    Directory of Open Access Journals (Sweden)

    Ueno Kazuko

    2009-04-01

    Full Text Available Abstract Background Model checking approaches were applied to biological pathway validations around 2003. Recently, Fisher et al. have proved the importance of model checking approach by inferring new regulation of signaling crosstalk in C. elegans and confirming the regulation with biological experiments. They took a discrete and state-based approach to explore all possible states of the system underlying vulval precursor cell (VPC fate specification for desired properties. However, since both discrete and continuous features appear to be an indispensable part of biological processes, it is more appropriate to use quantitative models to capture the dynamics of biological systems. Our key motivation of this paper is to establish a quantitative methodology to model and analyze in silico models incorporating the use of model checking approach. Results A novel method of modeling and simulating biological systems with the use of model checking approach is proposed based on hybrid functional Petri net with extension (HFPNe as the framework dealing with both discrete and continuous events. Firstly, we construct a quantitative VPC fate model with 1761 components by using HFPNe. Secondly, we employ two major biological fate determination rules – Rule I and Rule II – to VPC fate model. We then conduct 10,000 simulations for each of 48 sets of different genotypes, investigate variations of cell fate patterns under each genotype, and validate the two rules by comparing three simulation targets consisting of fate patterns obtained from in silico and in vivo experiments. In particular, an evaluation was successfully done by using our VPC fate model to investigate one target derived from biological experiments involving hybrid lineage observations. However, the understandings of hybrid lineages are hard to make on a discrete model because the hybrid lineage occurs when the system comes close to certain thresholds as discussed by Sternberg and Horvitz in

  1. Neurobiology of Caenorhabditis elegans Locomotion: Where Do We Stand?

    OpenAIRE

    Gjorgjieva, Julijana; Biron, David; Haspel, Gal

    2014-01-01

    Animals use a nervous system for locomotion in some stage of their life cycle. The nematode Caenorhabditis elegans, a major animal model for almost all fields of experimental biology, has long been used for detailed studies of genetic and physiological locomotion mechanisms. Of its 959 somatic cells, 302 are neurons that are identifiable by lineage, location, morphology, and neurochemistry in every adult hermaphrodite. Of those, 75 motoneurons innervate body wall muscles that provide the thru...

  2. Lycopene attenuates Aβ1-42 secretion and its toxicity in human cell and Caenorhabditis elegans models of Alzheimer disease.

    Science.gov (United States)

    Chen, Wei; Mao, Liuqun; Xing, Huanhuan; Xu, Lei; Fu, Xiang; Huang, Liyingzi; Huang, Dongling; Pu, Zhijun; Li, Qinghua

    2015-11-03

    Growing evidence suggests concentration of lycopene was reduced in plasma of patients with Alzheimer disease (AD). Lycopene, a member of the carotenoid family, has been identified as an antioxidant to attenuate oxidative damage and has neuroprotective role in several AD models. However, whether lycopene is involved in the pathogenesis of AD and molecular underpinnings are elusive. In this study, we found that lycopene can significantly delay paralysis in the Aβ1-42-transgenic Caenorhabditis elegans strain GMC101. Lycopene treatment reduced Aβ1-42 secretion in SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw). Next, we found lycopene can down-regulate expression level of β-amyloid precursor protein(APP) in APPsw cells. Moreover, lycopene treatment can not change endogenous reactive oxygen species level and apoptosis in APPsw cells. However, lycopene treatment protected against H2O2-induced oxidative stress and copper-induced damage in APPsw cells. Collectively, our data support that elevated lycopene contributes to the lower pathogenesis of AD. Our findings suggest that increasing lycopene in neurons may be a novel approach to attenuate onset and development of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Rapid experimental evolution of pesticide resistance in C. elegans entails no costs and affects the mating system.

    Directory of Open Access Journals (Sweden)

    Patricia C Lopes

    Full Text Available Pesticide resistance is a major concern in natural populations and a model trait to study adaptation. Despite the importance of this trait, the dynamics of its evolution and of its ecological consequences remain largely unstudied. To fill this gap, we performed experimental evolution with replicated populations of Caenorhabditis elegans exposed to the pesticide Levamisole during 20 generations. Exposure to Levamisole resulted in decreased survival, fecundity and male frequency, which declined from 30% to zero. This was not due to differential susceptibility of males. Rather, the drug affected mobility, resulting in fewer encounters, probably leading to reduced outcrossing rates. Adaptation, i.e., increased survival and fecundity, occurred within 10 and 20 generations, respectively. Male frequency also increased by generation 20. Adaptation costs were undetected in the ancestral environment and in presence of Ivermectin, another widely-used pesticide with an opposite physiological effect. Our results demonstrate that pesticide resistance can evolve at an extremely rapid pace. Furthermore, we unravel the effects of behaviour on life-history traits and test the environmental dependence of adaptation costs. This study establishes experimental evolution as a powerful tool to tackle pesticide resistance, and paves the way to further investigations manipulating environmental and/or genetic factors underlying adaptation to pesticides.

  4. Sex Pheromones of C. elegans Males Prime the Female Reproductive System and Ameliorate the Effects of Heat Stress.

    Directory of Open Access Journals (Sweden)

    Erin Z Aprison

    2015-12-01

    Full Text Available Pheromones are secreted molecules that mediate animal communications. These olfactory signals can have substantial effects on physiology and likely play important roles in organismal survival in natural habitats. Here we show that a blend of two ascaroside pheromones produced by C. elegans males primes the female reproductive system in part by improving sperm guidance toward oocytes. Worms have different physiological responses to different ratios of the same two molecules, revealing an efficient mechanism for increasing coding potential of a limited repertoire of molecular signals. The endogenous function of the male sex pheromones has an important side benefit. It substantially ameliorates the detrimental effects of prolonged heat stress on hermaphrodite reproduction because it increases the effectiveness with which surviving gametes are used following stress. Hermaphroditic species are expected to lose female-specific traits in the course of evolution. Our results suggest that some of these traits could have serendipitous utility due to their ability to counter the effects of stress. We propose that this is a general mechanism by which some mating-related functions could be retained in hermaphroditic species, despite their expected decay.

  5. Sex Pheromones of C. elegans Males Prime the Female Reproductive System and Ameliorate the Effects of Heat Stress

    Science.gov (United States)

    Aprison, Erin Z.; Ruvinsky, Ilya

    2015-01-01

    Pheromones are secreted molecules that mediate animal communications. These olfactory signals can have substantial effects on physiology and likely play important roles in organismal survival in natural habitats. Here we show that a blend of two ascaroside pheromones produced by C. elegans males primes the female reproductive system in part by improving sperm guidance toward oocytes. Worms have different physiological responses to different ratios of the same two molecules, revealing an efficient mechanism for increasing coding potential of a limited repertoire of molecular signals. The endogenous function of the male sex pheromones has an important side benefit. It substantially ameliorates the detrimental effects of prolonged heat stress on hermaphrodite reproduction because it increases the effectiveness with which surviving gametes are used following stress. Hermaphroditic species are expected to lose female-specific traits in the course of evolution. Our results suggest that some of these traits could have serendipitous utility due to their ability to counter the effects of stress. We propose that this is a general mechanism by which some mating-related functions could be retained in hermaphroditic species, despite their expected decay. PMID:26645097

  6. Untwisting the Caenorhabditis elegans embryo

    OpenAIRE

    Christensen, Ryan Patrick; Bokinsky, Alexandra; Santella, Anthony; Wu, Yicong; Marquina-Solis, Javier; Guo, Min; Kovacevic, Ismar; Kumar, Abhishek; Winter, Peter W; Tashakkori, Nicole; McCreedy, Evan; Liu, Huafeng; McAuliffe, Matthew; Mohler, William; Col?n-Ramos, Daniel A

    2015-01-01

    eLife digest Understanding how the brain and nervous system develops from a few cells into complex, interconnected networks is a key goal for neuroscientists. Although researchers have identified many of the genes involved in this process, how these work together to form an entire brain remains unknown. A simple worm called Caenorhabiditis elegans is commonly used to study brain development because it has only about 300 neurons, simplifying the study of its nervous system. The worms are easy ...

  7. Appetitive Olfactory Learning and Long-Term Associative Memory in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Ichiro N. Maruyama

    2017-05-01

    Full Text Available Because of the relative simplicity of its nervous system, Caenorhabditis elegans is a useful model organism to study learning and memory at cellular and molecular levels. For appetitive conditioning in C. elegans, food has exclusively been used as an unconditioned stimulus (US. It may be difficult to analyze neuronal circuits for associative memory since food is a multimodal combination of olfactory, gustatory, and mechanical stimuli. Here, we report classical appetitive conditioning and associative memory in C. elegans, using 1-nonanol as a conditioned stimulus (CS, and potassium chloride (KCl as a US. Before conditioning, C. elegans innately avoided 1-nonanol, an aversive olfactory stimulus, and was attracted by KCl, an appetitive gustatory stimulus, on assay agar plates. Both massed training without an intertrial interval (ITI and spaced training with a 10-min ITI induced significant levels of memory of association regarding the two chemicals. Memory induced by massed training decayed within 6 h, while that induced by spaced training was retained for more than 6 h. Animals treated with inhibitors of transcription or translation formed the memory induced by spaced training less efficiently than untreated animals, whereas the memory induced by massed training was not significantly affected by such treatments. By definition, therefore, memories induced by massed training and spaced training are classified as short-term memory (STM and long-term memory (LTM, respectively. When animals conditioned by spaced training were exposed to 1-nonanol alone, their learning index was lower than that of untreated animals, suggesting that extinction learning occurs in C. elegans. In support of these results, C. elegans mutants defective in nmr-1, encoding an NMDA receptor subunit, formed both STM and LTM less efficiently than wild-type animals, while mutations in crh-1, encoding a ubiquitous transcription factor CREB required for memory consolidation, affected

  8. PKA/KIN-1 mediates innate immune responses to bacterial pathogens in Caenorhabditis elegans.

    Science.gov (United States)

    Xiao, Yi; Liu, Fang; Zhao, Pei-Ji; Zou, Cheng-Gang; Zhang, Ke-Qin

    2017-11-01

    The genetically tractable organism Caenorhabditis elegans is a powerful model animal for the study of host innate immunity. Although the intestine and the epidermis of C. elegans that is in contact with pathogens are likely to function as sites for the immune function, recent studies indicate that the nervous system could control innate immunity in C. elegans. In this report, we demonstrated that protein kinase A (PKA)/KIN-1 in the neurons contributes to resistance against Salmonella enterica infection in C. elegans. Microarray analysis revealed that PKA/KIN-1 regulates the expression of a set of antimicrobial effectors in the non-neuron tissues, which are required for innate immune responses to S. enterica. Furthermore, PKA/KIN-1 regulated the expression of lysosomal genes during S. enterica infection. Our results suggest that the lysosomal signaling molecules are involved in autophagy by controlling autophagic flux, rather than formation of autophagosomes. As autophagy is crucial for host defense against S. enterica infection in a metazoan, the lysosomal pathway also acts as a downstream effector of the PKA/KIN-1 signaling for innate immunity. Our data indicate that the PKA pathway contributes to innate immunity in C. elegans by signaling from the nervous system to periphery tissues to protect the host against pathogens.

  9. Use of the induced gene-expression in the soil nematode Caenorhabditis elegans as a biomonitor; Nutzung der induzierbaren Genexpression des Nematoden Caenorhabditis elegans als Biomonitor

    Energy Technology Data Exchange (ETDEWEB)

    Menzel, R.; Reichert, K.; Achazi, R. [Freie Univ. Berlin (Germany). Inst. fuer Biologie - Oekotoxikologie und Biochemie

    2002-07-01

    The soil nematode Caenorhabditis elegans is one of the simplest animals having the status of a laboratory model. Its already completely sequenced genome contains the remarkable number of 80 cytochrome P450 genes (CYP) and many further genes coding for enzymes involved in biotransformation. In order to study xenobiotically induced gene expression in C. elegans, liquid cultures were exposed to different, well-known xenobiotic inducers. The mRNA expression was detected by two different types of DNA arrays and semi-quantitative RT-PCR. {beta}-naphthoflavone, PCB52 and lansoprazol were the most active and, in particular, induced almost all CYP35 isoforms strongly. In conclusion, the xenobiotic dependent gene expression of C. elegans is a useful tool to reveal defense mechanisms against potential damaging substances as well as for developing a biomonitoring system. (orig.) [German] Der Bodennematode Caenorhabditis elegans gilt als das einfachste mehrzellige Tier mit dem Status eines Labormodels. Basierend auf seinem entschluesselten Genom konnte die bemerkenswerte Zahl von 80 Cytochrom P450 Genen (CYP) und eine Vielzahl weiterer Gene, welche fuer Enzyme der Biotransformation kodieren, identifiziert werden. Die differentielle Genexpression von C. elegans nach Schadstoffzugabe wurde in Fluessigkulturen mit 18 Xenobiotika aus unterschiedlichen Schadstoffgruppen untersucht. Anschliessend wurde die mRNA Expression mit DNA Arrays und semi-quantitativer RT-PCR bestimmt. {beta}-Naphthoflavone, PCB52 and Lansoprazol erwiesen sich dabei als die wirksamsten Induktoren und konnten unter anderen alle CYP 35 Isoformen stark induzieren. Mit diesen Untersuchungen konnte gezeigt werden, dass die schadstoffinduzierte Genexpression in C. elegans ein adaequates System ist, um sowohl Detoxifikationsmechanismen zu untersuchen als auch ein Biomonitorscreening aufzubauen. (orig.)

  10. Approaches for Studying Autophagy in Caenorhabditis elegans

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    Yanfang Chen

    2017-08-01

    Full Text Available Macroautophagy (hereafter referred to as autophagy is an intracellular degradative process, well conserved among eukaryotes. By engulfing cytoplasmic constituents into the autophagosome for degradation, this process is involved in the maintenance of cellular homeostasis. Autophagy induction triggers the formation of a cup-shaped double membrane structure, the phagophore, which progressively elongates and encloses materials to be removed. This double membrane vesicle, which is called an autophagosome, fuses with lysosome and forms the autolysosome. The inner membrane of the autophagosome, along with engulfed compounds, are degraded by lysosomal enzymes, which enables the recycling of carbohydrates, amino acids, nucleotides, and lipids. In response to various factors, autophagy can be induced for non-selective degradation of bulk cytoplasm. Autophagy is also able to selectively target cargoes and organelles such as mitochondria or peroxisome, functioning as a quality control system. The modification of autophagy flux is involved in developmental processes such as resistance to stress conditions, aging, cell death, and multiple pathologies. So, the use of animal models is essential for understanding these processes in the context of different cell types throughout the entire lifespan. For almost 15 years, the nematode Caenorhabditis elegans has emerged as a powerful model to analyze autophagy in physiological or pathological contexts. This review presents a rapid overview of physiological processes involving autophagy in Caenorhabditis elegans, the different assays used to monitor autophagy, their drawbacks, and specific tools for the analyses of selective autophagy.

  11. Studying Human Disease Genes in "Caenorhabditis Elegans": A Molecular Genetics Laboratory Project

    Science.gov (United States)

    Cox-Paulson, Elisabeth A.; Grana, Theresa M.; Harris, Michelle A.; Batzli, Janet M.

    2012-01-01

    Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether "Caenorhabditis elegans" can be a useful model system for studying genes…

  12. Dopamine Receptor DOP-4 Modulates Habituation to Repetitive Photoactivation of a "C. elegans" Polymodal Nociceptor

    Science.gov (United States)

    Ardiel, Evan L.; Giles, Andrew C.; Yu, Alex J.; Lindsay, Theodore H.; Lockery, Shawn R.; Rankin, Catharine H.

    2016-01-01

    Habituation is a highly conserved phenomenon that remains poorly understood at the molecular level. Invertebrate model systems, like "Caenorhabditis elegans," can be a powerful tool for investigating this fundamental process. Here we established a high-throughput learning assay that used real-time computer vision software for behavioral…

  13. Closing in on the C. elegans ORFeome by cloning TWINSCAN predictions

    DEFF Research Database (Denmark)

    Wei, Chaochun; Lamesch, Philippe; Arumugam, Manimozhiyan

    2005-01-01

    The genome of Caenorhabditis elegans was the first animal genome to be sequenced. Although considerable effort has been devoted to annotating it, the standard WormBase annotation contains thousands of predicted genes for which there is no cDNA or EST evidence. We hypothesized that a more complete...... experimental annotation could be obtained by creating a more accurate gene-prediction program and then amplifying and sequencing predicted genes. Our approach was to adapt the TWINSCAN gene prediction system to C. elegans and C. briggsae and to improve its splice site and intron-length models. The resulting...... be significantly increased by replacing its partially curated predicted genes with TWINSCAN predictions. The technology described in this study will continue to drive the C. elegans ORFeome toward completion and contribute to the annotation of the three Caenorhabditis species currently being sequenced. The results...

  14. The Nucleolus of Caenorhabditis elegans

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    Li-Wei Lee

    2012-01-01

    Full Text Available Nucleolar size and appearance correlate with ribosome biogenesis and cellular activity. The mechanisms underlying changes in nucleolar appearance and regulation of nucleolar size that occur during differentiation and cell cycle progression are not well understood. Caenorhabditis elegans provides a good model for studying these processes because of its small size and transparent body, well-characterized cell types and lineages, and because its cells display various sizes of nucleoli. This paper details the advantages of using C. elegans to investigate features of the nucleolus during the organism's development by following dynamic changes in fibrillarin (FIB-1 in the cells of early embryos and aged worms. This paper also illustrates the involvement of the ncl-1 gene and other possible candidate genes in nucleolar-size control. Lastly, we summarize the ribosomal proteins involved in life span and innate immunity, and those homologous genes that correspond to human disorders of ribosomopathy.

  15. Tat-mediated protein delivery in living Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Delom, Frederic; Fessart, Delphine; Caruso, Marie-Elaine; Chevet, Eric

    2007-01-01

    The Tat protein from HIV-1 fused with heterologous proteins traverses biological membranes in a transcellular process called: protein transduction. This has already been successfully exploited in various biological models, but never in the nematode worm Caenorhabditis elegans. TAT-eGFP or GST-eGFP proteins were fed to C. elegans worms, which resulted in the specific localization of Tat-eGFP to epithelial intestinal cells. This system represents an efficient tool for transcellular transduction in C. elegans intestinal cells. Indeed, this approach avoids the use of tedious purification steps to purify the TAT fusion proteins and allows for rapid analyses of the transduced proteins. In addition, it may represent an efficient tool to functionally analyze the mechanisms of protein transduction as well as to complement RNAi/KO in the epithelial intestinal system. To sum up, the advantage of this technology is to combine the potential of bacterial expression system and the Tat-mediated transduction technique in living worm

  16. Caenorhabditis elegans intersectin: a synaptic protein regulating neurotransmission

    DEFF Research Database (Denmark)

    Rose, Simon; Malabarba, Maria Grazia; Krag, Claudia

    2007-01-01

    the characterization of intersectin function in Caenorhabditis elegans. Nematode intersectin (ITSN-1) is expressed in the nervous system, and it is enriched in presynaptic regions. The C. elegans intersectin gene (itsn-1) is nonessential for viability. In addition, itsn-1-null worms do not display any evident...

  17. Alcohol disinhibition of behaviors in C. elegans.

    Directory of Open Access Journals (Sweden)

    Stephen M Topper

    Full Text Available Alcohol has a wide variety of effects on physiology and behavior. One of the most well-recognized behavioral effects is disinhibition, where behaviors that are normally suppressed are displayed following intoxication. A large body of evidence has shown that alcohol-induced disinhibition in humans affects attention, verbal, sexual, and locomotor behaviors. Similar behavioral disinhibition is also seen in many animal models of ethanol response, from invertebrates to mammals and primates. Here we describe several examples of disinhibition in the nematode C. elegans. The nematode displays distinct behavioral states associated with locomotion (crawling on land and swimming in water that are mediated by dopamine. On land, animals crawl and feed freely, but these behaviors are inhibited in water. We found that additional behaviors, including a variety of escape responses are also inhibited in water. Whereas alcohol non-specifically impaired locomotion, feeding, and escape responses in worms on land, alcohol specifically disinhibited these behaviors in worms immersed in water. Loss of dopamine signaling relieved disinhibition of feeding behavior, while loss of the D1-like dopamine receptor DOP-4 impaired the ethanol-induced disinhibition of crawling. The powerful genetics and simple nervous system of C. elegans may help uncover conserved molecular mechanisms that underlie alcohol-induced disinhibition of behaviors in higher animals.

  18. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yinxia Li

    Full Text Available Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  19. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

    Science.gov (United States)

    Li, Yinxia; Zhao, Yunli; Huang, Xu; Lin, Xingfeng; Guo, Yuling; Wang, Daoyong; Li, Chaojun; Wang, Dayong

    2013-01-01

    Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  20. Serotonin Control of Thermotaxis Memory Behavior in Nematode Caenorhabditis elegans

    Science.gov (United States)

    Guo, Yuling; Wang, Daoyong; Li, Chaojun; Wang, Dayong

    2013-01-01

    Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans. PMID:24223727

  1. Immobilization of Caenorhabditis elegans to Analyze Intracellular Transport in Neurons.

    Science.gov (United States)

    Niwa, Shinsuke

    2017-10-18

    Axonal transport and intraflagellar transport (IFT) are essential for axon and cilia morphogenesis and function. Kinesin superfamily proteins and dynein are molecular motors that regulate anterograde and retrograde transport, respectively. These motors use microtubule networks as rails. Caenorhabditis elegans (C. elegans) is a powerful model organism to study axonal transport and IFT in vivo. Here, I describe a protocol to observe axonal transport and IFT in living C. elegans. Transported cargo can be visualized by tagging cargo proteins using fluorescent proteins such as green fluorescent protein (GFP). C. elegans is transparent and GFP-tagged cargo proteins can be expressed in specific cells under cell-specific promoters. Living worms can be fixed by microbeads on 10% agarose gel without killing or anesthetizing the worms. Under these conditions, cargo movement can be directly observed in the axons and cilia of living C. elegans without dissection. This method can be applied to the observation of any cargo molecule in any cells by modifying the target proteins and/or the cells they are expressed in. Most basic proteins such as molecular motors and adaptor proteins that are involved in axonal transport and IFT are conserved in C. elegans. Compared to other model organisms, mutants can be obtained and maintained more easily in C. elegans. Combining this method with various C. elegans mutants can clarify the molecular mechanisms of axonal transport and IFT.

  2. A mutational analysis of Caenorhabditis elegans in space

    International Nuclear Information System (INIS)

    Zhao Yang; Lai, Kenneth; Cheung, Iris; Youds, Jillian; Tarailo, Maja; Tarailo, Sanja; Rose, Ann

    2006-01-01

    The International Caenorhabditis elegans Experiment First Flight (ICE-First) was a project using C. elegans as a model organism to study the biological effects of short duration spaceflight (11 days in the International Space Station). As a member of the ICE-First research team, our group focused on the mutational effects of spaceflight. Several approaches were taken to measure mutational changes that occurred during the spaceflight including measurement of the integrity of poly-G/poly-C tracts, determination of the mutation frequency in the unc-22 gene, analysis of lethal mutations captured by the genetic balancer eT1(III;V), and identification of alterations in telomere length. By comparing the efficiency, sensitivity, and convenience of these methods, we deduced that the eT1 balancer system is well-suited for capturing, maintaining and recovering mutational events that occur over several generations during spaceflight. In the course of this experiment, we have extended the usefulness of the eT1 balancer system by identifying the physical breakpoints of the eT1 translocation and have developed a PCR assay to follow the eT1 chromosomes. C. elegans animals were grown in a defined liquid media during the spaceflight. This is the first analysis of genetic changes in C. elegans grown in the defined media. Although no significant difference in mutation rate was detected between spaceflight and control samples, which is not surprising given the short duration of the spaceflight, we demonstrate here the utility of worms as an integrating biological dosimeter for spaceflight

  3. A mutational analysis of Caenorhabditis elegans in space

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Yang [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Lai, Kenneth [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Cheung, Iris [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Youds, Jillian [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Tarailo, Maja [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Tarailo, Sanja [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Rose, Ann [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada)]. E-mail: arose@gene.nce.ubc.ca

    2006-10-10

    The International Caenorhabditis elegans Experiment First Flight (ICE-First) was a project using C. elegans as a model organism to study the biological effects of short duration spaceflight (11 days in the International Space Station). As a member of the ICE-First research team, our group focused on the mutational effects of spaceflight. Several approaches were taken to measure mutational changes that occurred during the spaceflight including measurement of the integrity of poly-G/poly-C tracts, determination of the mutation frequency in the unc-22 gene, analysis of lethal mutations captured by the genetic balancer eT1(III;V), and identification of alterations in telomere length. By comparing the efficiency, sensitivity, and convenience of these methods, we deduced that the eT1 balancer system is well-suited for capturing, maintaining and recovering mutational events that occur over several generations during spaceflight. In the course of this experiment, we have extended the usefulness of the eT1 balancer system by identifying the physical breakpoints of the eT1 translocation and have developed a PCR assay to follow the eT1 chromosomes. C. elegans animals were grown in a defined liquid media during the spaceflight. This is the first analysis of genetic changes in C. elegans grown in the defined media. Although no significant difference in mutation rate was detected between spaceflight and control samples, which is not surprising given the short duration of the spaceflight, we demonstrate here the utility of worms as an integrating biological dosimeter for spaceflight.

  4. Microfluidic Devices in Advanced Caenorhabditis elegans Research

    Directory of Open Access Journals (Sweden)

    Muniesh Muthaiyan Shanmugam

    2016-08-01

    Full Text Available The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, therefore, studies on C. elegans can be translated to human, as well as, C. elegans can be used in the study of different types of parasitic worms that infect other living organisms. In the past decade, many efforts have been undertaken to establish interdisciplinary research collaborations between biologists, physicists and engineers in order to develop microfluidic devices to study the biology of C. elegans. Microfluidic devices with the power to manipulate and detect bio-samples, regents or biomolecules in micro-scale environments can well fulfill the requirement to handle worms under proper laboratory conditions, thereby significantly increasing research productivity and knowledge. The recent development of different kinds of microfluidic devices with ultra-high throughput platforms has enabled researchers to carry out worm population studies. Microfluidic devices primarily comprises of chambers, channels and valves, wherein worms can be cultured, immobilized, imaged, etc. Microfluidic devices have been adapted to study various worm behaviors, including that deepen our understanding of neuromuscular connectivity and functions. This review will provide a clear account of the vital involvement of microfluidic devices in worm biology.

  5. Genome-wide identification of Pseudomonas aeruginosa virulence-related genes using a Caenorhabditis elegans infection model.

    Directory of Open Access Journals (Sweden)

    Rhonda L Feinbaum

    Full Text Available Pseudomonas aeruginosa strain PA14 is an opportunistic human pathogen capable of infecting a wide range of organisms including the nematode Caenorhabditis elegans. We used a non-redundant transposon mutant library consisting of 5,850 clones corresponding to 75% of the total and approximately 80% of the non-essential PA14 ORFs to carry out a genome-wide screen for attenuation of PA14 virulence in C. elegans. We defined a functionally diverse 180 mutant set (representing 170 unique genes necessary for normal levels of virulence that included both known and novel virulence factors. Seven previously uncharacterized virulence genes (ABC transporters PchH and PchI, aminopeptidase PepP, ATPase/molecular chaperone ClpA, cold shock domain protein PA0456, putative enoyl-CoA hydratase/isomerase PA0745, and putative transcriptional regulator PA14_27700 were characterized with respect to pigment production and motility and all but one of these mutants exhibited pleiotropic defects in addition to their avirulent phenotype. We examined the collection of genes required for normal levels of PA14 virulence with respect to occurrence in P. aeruginosa strain-specific genomic regions, location on putative and known genomic islands, and phylogenetic distribution across prokaryotes. Genes predominantly contributing to virulence in C. elegans showed neither a bias for strain-specific regions of the P. aeruginosa genome nor for putatively horizontally transferred genomic islands. Instead, within the collection of virulence-related PA14 genes, there was an overrepresentation of genes with a broad phylogenetic distribution that also occur with high frequency in many prokaryotic clades, suggesting that in aggregate the genes required for PA14 virulence in C. elegans are biased towards evolutionarily conserved genes.

  6. Genome-wide identification of Pseudomonas aeruginosa virulence-related genes using a Caenorhabditis elegans infection model.

    Science.gov (United States)

    Feinbaum, Rhonda L; Urbach, Jonathan M; Liberati, Nicole T; Djonovic, Slavica; Adonizio, Allison; Carvunis, Anne-Ruxandra; Ausubel, Frederick M

    2012-01-01

    Pseudomonas aeruginosa strain PA14 is an opportunistic human pathogen capable of infecting a wide range of organisms including the nematode Caenorhabditis elegans. We used a non-redundant transposon mutant library consisting of 5,850 clones corresponding to 75% of the total and approximately 80% of the non-essential PA14 ORFs to carry out a genome-wide screen for attenuation of PA14 virulence in C. elegans. We defined a functionally diverse 180 mutant set (representing 170 unique genes) necessary for normal levels of virulence that included both known and novel virulence factors. Seven previously uncharacterized virulence genes (ABC transporters PchH and PchI, aminopeptidase PepP, ATPase/molecular chaperone ClpA, cold shock domain protein PA0456, putative enoyl-CoA hydratase/isomerase PA0745, and putative transcriptional regulator PA14_27700) were characterized with respect to pigment production and motility and all but one of these mutants exhibited pleiotropic defects in addition to their avirulent phenotype. We examined the collection of genes required for normal levels of PA14 virulence with respect to occurrence in P. aeruginosa strain-specific genomic regions, location on putative and known genomic islands, and phylogenetic distribution across prokaryotes. Genes predominantly contributing to virulence in C. elegans showed neither a bias for strain-specific regions of the P. aeruginosa genome nor for putatively horizontally transferred genomic islands. Instead, within the collection of virulence-related PA14 genes, there was an overrepresentation of genes with a broad phylogenetic distribution that also occur with high frequency in many prokaryotic clades, suggesting that in aggregate the genes required for PA14 virulence in C. elegans are biased towards evolutionarily conserved genes.

  7. Screening for bioactivity of Mutinus elegans extracts

    Science.gov (United States)

    Gajendiran, A.; Cyriac, RE; Abraham, J.

    2017-11-01

    Mutinus elegans is a species of fungi that is commonly called as Elegant Stinkhorn. The aim of this study was to screen the crude extracts of the fungus for phytochemical analysis, antimicrobial activity, antioxidant assay and anticancer activity. Extraction of the fungal sample in Soxhlet apparatus was done with n-hexane and methanol as the solvent. Stock solutions of the crude methanol extract were prepared and used for microbiological assay. Thin layer chromatography was performed in order to determine the number of active components in n-hexane, and methanol solvent system for the fungus Mutinus elegans. Further, antioxidant assay was performed using DPPH radical scavenging assay. The fungal sample was then tested for cytotoxicity assay against MG63 osteosarcoma cell lines. The antimicrobial assay of Mutinus elegans extract exhibited activity against five pathogens. The zone of inhibition was measured with respect to standard antibiotics. Gas chromatography and Mass spectrometry (GC/MS analysis), revealed the presence of dibromo-tetradecan-1-ol-acetate, 2-myristynoyl-glycinamide, fumaric acid, and cyclohexylmethyldecyl ester compounds were presented in methanol and n-hexane extract of Mutinus elegans. The present study concludes the presence of bioactive compound in the extract which exhibited antimicrobial and antioxidant activity in Mutinus elegans.

  8. DPY-17 and MUA-3 Interact for Connective Tissue-Like Tissue Integrity in Caenorhabditis elegans: A Model for Marfan Syndrome.

    Science.gov (United States)

    Fotopoulos, Pauline; Kim, Jeongho; Hyun, Moonjung; Qamari, Waiss; Lee, Inhwan; You, Young-Jai

    2015-04-27

    mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3 that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated mutations in dpy-17 as a suppressor. RNAi of dpy-17 in mua-3 rescued the lethality, confirming dpy-17 is a suppressor. dpy-17 encodes a collagen known to genetically interact with dpy-31, a BMP-1/Tolloid-like metalloprotease required for TGFβ activation in mammals. Human fibrillin1 mutants fail to sequester TGFβ2 leading to excess TGFβ signaling, which in turn contributes to Marfan syndrome or Marfan-related syndrome. Consistent with that, RNAi of dbl-1, a TGFβ homolog, modestly rescued the lethality of mua-3 mutants, suggesting a potentially conserved interaction between MUA-3 and a TGFβ pathway in C. elegans. Our work provides genetic evidence of the interaction between TGFβ and a fibrillin homolog, and thus provides a simple yet powerful genetic model to study TGFβ function in development of Marfan pathology. Copyright © 2015 Fotopoulos et al.

  9. An efficient transgenic system by TA cloning vectors and RNAi for C. elegans

    International Nuclear Information System (INIS)

    Gengyo-Ando, Keiko; Yoshina, Sawako; Inoue, Hideshi; Mitani, Shohei

    2006-01-01

    In the nematode, transgenic analyses have been performed by microinjection of DNA from various sources into the syncytium gonad. To expedite these transgenic analyses, we solved two potential problems in this work. First, we constructed an efficient TA-cloning vector system which is useful for any promoter. By amplifying the genomic DNA fragments which contain regulatory sequences with or without the coding region, we could easily construct plasmids expressing fluorescent protein fusion without considering restriction sites. We could dissect motor neurons with three colors in a single animal. Second, we used feeding RNAi to isolate transgenic strains which express lag-2::venus fusion gene. We found that the fusion protein is toxic when ectopically expressed in embryos but is functional to rescue a loss of function mutant in the lag-2 gene. Thus, the transgenic system described here should be useful to examine the protein function in the nematode

  10. IMPACT OF FOOD AND FOLATE SUPPLEMENTATION DURING Salmonella TYPHI INFECTION IN Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Bhagavathi Sundaram Sivamaruthi

    2012-06-01

    Full Text Available Caenorhabditis elegans is an instructive and suitable model for studying pathogenesis of almost all human pathogens. Salmonella Typhi is gram-negative facultative intracellular anaerobe that causes several pathetic infections. Necessary enriched nutrient ingestion during pathological conditions may reduce the harshness of the infection. We investigated the impact of folate and food supplementation during S. Typhi infection on the model system, C. elegans. Our data indicated that folate supplementation (10 µg increases the lifespan of S. Typhi infected C. elegans up to 20%. In combination with laboratory food source E. coli OP50, folate increases the infected the worm’s lifespan to 40%. The wild type C. elegans infected by S. Typhi died with the LT50 of 60 ± 12 h. The LT50 of S. Typhi infected folt-1 mutant strain VC959 was 96 ± 6 h. However, the folate supplemented mutant worms exhibited an extended life with LT50 of 120 ± 6 h. The short time exposure and pharyngeal pumping studies confirmed that folt-1 mutant worm exhibited increased survival rate during pathogenic course at significant level when compared to wild-type. Our data revealed that folt-1 plays a significant role in host defense system against S. Typhi infection and the folate supplementation in combination with food increases the host survival during S. Typhi infection.

  11. The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans during bacterial infection, by modulating the nematode's innate immune response.

    Directory of Open Access Journals (Sweden)

    Henrik Jakobsen

    Full Text Available The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes. We also found that the expression of the putative immune effector gene F35E12.5 was up-regulated in response to Harmane treatment. This indicates that Harmane stimulates the innate immune response of the nematode; thereby increasing its lifespan during bacterial infection. Expression of F35E12.5 is predominantly regulated through the p38 MAPK pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This indicates that Harmane has a complex effect on the innate immune system of C. elegans. Harmane could therefore be a useful tool in the further research into C. elegans immunity. Since the innate immunity of C. elegans has a high degree of evolutionary conservation, drugs such as Harmane could also be possible alternatives to classic antibiotics. The C. elegans model could prove to be useful for selection and development of such drugs.

  12. The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans during bacterial infection, by modulating the nematode's innate immune response.

    Science.gov (United States)

    Jakobsen, Henrik; Bojer, Martin S; Marinus, Martin G; Xu, Tao; Struve, Carsten; Krogfelt, Karen A; Løbner-Olesen, Anders

    2013-01-01

    The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes. We also found that the expression of the putative immune effector gene F35E12.5 was up-regulated in response to Harmane treatment. This indicates that Harmane stimulates the innate immune response of the nematode; thereby increasing its lifespan during bacterial infection. Expression of F35E12.5 is predominantly regulated through the p38 MAPK pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This indicates that Harmane has a complex effect on the innate immune system of C. elegans. Harmane could therefore be a useful tool in the further research into C. elegans immunity. Since the innate immunity of C. elegans has a high degree of evolutionary conservation, drugs such as Harmane could also be possible alternatives to classic antibiotics. The C. elegans model could prove to be useful for selection and development of such drugs.

  13. Aging Effects of Caenorhabditis elegans Ryanodine Receptor Variants Corresponding to Human Myopathic Mutations

    Directory of Open Access Journals (Sweden)

    Katie Nicoll Baines

    2017-05-01

    Full Text Available Delaying the decline in skeletal muscle function will be critical to better maintenance of an active lifestyle in old age. The skeletal muscle ryanodine receptor, the major intracellular membrane channel through which calcium ions pass to elicit muscle contraction, is central to calcium ion balance and is hypothesized to be a significant factor for age-related decline in muscle function. The nematode Caenorhabditis elegans is a key model system for the study of human aging, and strains were generated with modified C. elegans ryanodine receptors corresponding to human myopathic variants linked with malignant hyperthermia and related conditions. The altered response of these strains to pharmacological agents reflected results of human diagnostic tests for individuals with these pathogenic variants. Involvement of nerve cells in the C. elegans responses may relate to rare medical symptoms concerning the central nervous system that have been associated with ryanodine receptor variants. These single amino acid modifications in C. elegans also conferred a reduction in lifespan and an accelerated decline in muscle integrity with age, supporting the significance of ryanodine receptor function for human aging.

  14. Modulation of Caenorhabditis elegans immune response and modification of Shigella endotoxin upon interaction.

    Science.gov (United States)

    Kesika, Periyanaina; Prasanth, Mani Iyer; Balamurugan, Krishnaswamy

    2015-04-01

    To analyze the pathogenesis at both physiological and molecular level using the model organism, Caenorhabditis elegans at different developmental stages in response to Shigella spp. and its pathogen associated molecular patterns such as lipopolysaccharide. The solid plate and liquid culture-based infection assays revealed that Shigella spp. infects C. elegans and had an impact on the brood size and pharyngeal pumping rate. LPS of Shigella spp. was toxic to C. elegans. qPCR analysis revealed that host innate immune genes have been modulated upon Shigella spp. infections and its LPS challenges. Non-destructive analysis was performed to kinetically assess the alterations in LPS during interaction of Shigella spp. with C. elegans. The modulation of innate immune genes attributed the surrendering of host immune system to Shigella spp. by favoring the infection. LPS appeared to have a major role in Shigella-mediated pathogenesis and Shigella employs a tactic behavior of modifying its LPS content to escape from the recognition of host immune system. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. of Caenorhabditis elegans: Adaptive and developmental regulation

    Indian Academy of Sciences (India)

    2015-04-27

    Apr 27, 2015 ... cursor for the synthesis of flavin adenine dinucleotide (FAD) ... an excellent animal model for performing integrated in vivo ..... amino acid sequence of C. elegans RFT-2 with human hRFT2 (RFVT3), rat rRFT2 and mice.

  16. Morphology of the bryozoan Cinctipora elegans (Cyclostomata, Cinctiporidae) with first data on its sexual reproduction and the cyclostome neuro-muscular system.

    Science.gov (United States)

    Schwaha, Thomas F; Handschuh, Stephan; Ostrovsky, Andrew N; Wanninger, Andreas

    2018-06-14

    Cyclostome bryozoans are an ancient group of marine colonial suspension-feeders comprising approximately 700 extant species. Previous morphological studies are mainly restricted to skeletal characters whereas data on soft tissues obtained by state-of-the-art methods are still lacking. In order to contribute to issues related to cyclostome ground pattern reconstruction, we analyzed the morphology of the neuromuscular system Cinctipora elegans by means of immunocytochemical staining, confocal laser scanning microscopy, histological sections and microCT imaging. Polypides of C. elegans are located in elongated tubular skeletal cystids. Distally, the orifice leads into a prominent vestibulum which is lined by an epithelium that joins an almost complete perimetrical attachment organ, both containing radially arranged neurite bundles and muscles. Centrally, the prominent atrial sphincter separates the vestibulum from the atrium. The latter is enclosed by the tentacle sheath which contains few longitudinal muscle fibers and two principal neurite bundles. These emerge from the cerebral ganglion, which is located at the lophophoral base. Lateral ganglia are located next to the cerebral ganglion from which the visceral neurite bundles emerge that extend proximally towards the foregut. There are four tentacle neurite bundles that emerge from the ganglia and the circum-oral nerve ring, which encompasses the pharynx. The tentacles possess two striated longitudinal muscles. Short buccal dilatators are situated at the lophophoral base and short muscular sets are present at the abfrontal and frontal side of the tentacle base. The pharynx is myoepithelial and triradiate in cross-section. Oocytes are found inside the pharyngeal myoepithelium. The digestive tract contains dense circular musculature and few longitudinal muscles. The membranous sac contains regular, thin, circular and diagonal muscles and neurites in its epithelial lining. The general structure of the neuro

  17. Caenorhabditis elegans reveals novel Pseudomonas aeruginosa virulence mechanism

    NARCIS (Netherlands)

    Utari, Putri Dwi; Quax, Wim J.

    The susceptibility of Caenorhabditis elegans to different virulent phenotypes of Pseudomonas aeruginosa makes the worms an excellent model for studying host-pathogen interactions. Including the recently described liquid killing, five different killing assays are now available offering superb

  18. Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium.

    Science.gov (United States)

    Pukkila-Worley, Read; Ausubel, Frederick M

    2012-02-01

    Intestinal epithelial cells provide an essential line of defense for Caernohabditis elegans against ingested pathogens. Because nematodes consume microorganisms as their food source, there has presumably been selection pressure to evolve and maintain immune defense mechanisms within the intestinal epithelium. Here we review recent advances that further define the immune signaling network within these cells and suggest mechanisms used by the nematode to monitor for infection. In reviewing studies of pathogenesis that use this simple model system, we hope to illustrate some of the basic principles of epithelial immunity that may also be of relevance in higher order hosts. Copyright © 2012. Published by Elsevier Ltd.

  19. Molecular control of memory in nematode Caenorhabditis elegans

    OpenAIRE

    Ye, Hua-Yue; Ye, Bo-Ping; Wang, Da-Yong

    2008-01-01

    Model invertebrate organism Caenorhabditis elegans has become an ideal model to unravel the complex processes of memory. C. elegans has three simple forms of memory: memory for thermosensation, memory for chemosensation, and memory for mechanosensation. In the form of memory for mechanosensation, short-term memory, intermediate-term memory, and long-term memory have been extensively studied. The short-term memory and intermediate-term memory may occur in the presynaptic sensory neurons, where...

  20. Investigating the Role of the Host Multidrug Resistance Associated Protein Transporter Family in Burkholderia cepacia Complex Pathogenicity Using a Caenorhabditis elegans Infection Model.

    Science.gov (United States)

    Tedesco, Pietro; Visone, Marco; Parrilli, Ermenegilda; Tutino, Maria Luisa; Perrin, Elena; Maida, Isabel; Fani, Renato; Ballestriero, Francesco; Santos, Radleigh; Pinilla, Clemencia; Di Schiavi, Elia; Tegos, George; de Pascale, Donatella

    2015-01-01

    This study investigated the relationship between host efflux system of the non-vertebrate nematode Caenorhabditis elegans and Burkholderia cepacia complex (Bcc) strain virulence. This is the first comprehensive effort to profile host-transporters within the context of Bcc infection. With this aim, two different toxicity tests were performed: a slow killing assay that monitors mortality of the host by intestinal colonization and a fast killing assay that assesses production of toxins. A Virulence Ranking scheme was defined, that expressed the toxicity of the Bcc panel members, based on the percentage of surviving worms. According to this ranking the 18 Bcc strains were divided in 4 distinct groups. Only the Cystic Fibrosis isolated strains possessed profound nematode killing ability to accumulate in worms' intestines. For the transporter analysis a complete set of isogenic nematode single Multidrug Resistance associated Protein (MRP) efflux mutants and a number of efflux inhibitors were interrogated in the host toxicity assays. The Bcc pathogenicity profile of the 7 isogenic C. elegans MRP knock-out strains functionality was classified in two distinct groups. Disabling host transporters enhanced nematode mortality more than 50% in 5 out of 7 mutants when compared to wild type. In particular mrp-2 was the most susceptible phenotype with increased mortality for 13 out 18 Bcc strains, whereas mrp-3 and mrp-4 knock-outs had lower mortality rates, suggesting a different role in toxin-substrate recognition. The use of MRP efflux inhibitors in the assays resulted in substantially increased (>40% on average) mortality of wild-type worms.

  1. A Computational Model Based on Multi-Regional Calcium Imaging Represents the Spatio-Temporal Dynamics in a Caenorhabditis elegans Sensory Neuron.

    Directory of Open Access Journals (Sweden)

    Masahiro Kuramochi

    Full Text Available Due to the huge number of neuronal cells in the brain and their complex circuit formation, computer simulation of neuronal activity is indispensable to understanding whole brain dynamics. Recently, various computational models have been developed based on whole-brain calcium imaging data. However, these analyses monitor only the activity of neuronal cell bodies and treat the cells as point unit. This point-neuron model is inexpensive in computational costs, but the model is unrealistically simplistic at representing intact neural activities in the brain. Here, we describe a novel three-unit Ordinary Differential Equation (ODE model based on the neuronal responses derived from a Caenorhabditis elegans salt-sensing neuron. We recorded calcium responses in three regions of the ASER neuron using a simple downstep of NaCl concentration. Our simple ODE model generated from a single recording can adequately reproduce and predict the temporal responses of each part of the neuron to various types of NaCl concentration changes. Our strategy which combines a simple recording data and an ODE mathematical model may be extended to realistically understand whole brain dynamics by computational simulation.

  2. A novel trapping system for the detection of reactive drug metabolites using the fungus Cunninghamella elegans and high resolution mass spectrometry.

    Science.gov (United States)

    Rydevik, Axel; Hansson, Annelie; Hellqvist, Anna; Bondesson, Ulf; Hedeland, Mikael

    2015-07-01

    A new model is presented that can be used to screen for bioactivation of drugs. The evaluation of toxicity is an important step in the development of new drugs. One way to detect possible toxic metabolites is to use trapping agents such as glutathione. Often human liver microsomes are used as a metabolic model in initial studies. However, there is a need for alternatives that are easy to handle, cheap, and can produce large amounts of metabolites. In the presented study, paracetamol, mefenamic acid, and diclofenac, all known to form reactive metabolites in humans, were incubated with the fungus Cunninghamella elegans and the metabolites formed were characterized with ultra high performance liquid chromatography coupled to a quadrupole time of flight mass spectrometer. Interestingly, glutathione conjugates formed by the fungus were observed for all three drugs and their retention times and MS/MS spectra matched those obtained in a comparative experiment with human liver microsomes. These findings clearly demonstrated that the fungus is a suitable trapping model for toxic biotransformation products. Cysteine conjugates of all three test drugs were also observed with high signal intensities in the fungal incubates, giving the model a further indicator of drug bioactivation. To our knowledge, this is the first demonstration of the use of a fungal model for the formation and trapping of reactive drug metabolites. The investigated model is cheap, easy to handle, it does not involve experimental animals and it can be scaled up to produce large amounts of metabolites. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Advanced Behavioral Analyses Show that the Presence of Food Causes Subtle Changes in C. elegans Movement

    OpenAIRE

    Angstman, Nicholas B.; Frank, Hans-Georg; Schmitz, Christoph

    2016-01-01

    As a widely used and studied model organism, Caenorhabditis elegans worms offer the ability to investigate implications of behavioral change. Although, investigation of C. elegans behavioral traits has been shown, analysis is often narrowed down to measurements based off a single point, and thus cannot pick up on subtle behavioral and morphological changes. In the present study videos were captured of four different C. elegans strains grown in liquid cultures and transferred to NGM-agar plate...

  4. In Vivo Inhibition of Lipid Accumulation in Caenorhabditis elegans

    Science.gov (United States)

    Sulistiyani; Purwakusumah, E. P.; Andrianto, D.

    2017-03-01

    This is a preliminary research report on the use of Caenorhabditis elegans as a model to establish anti-obesity screening assay of the natural plant resources. Nematode C. elegans has been used as experimental animal model for understanding lipid accumulation. The objective of this research was to investigate the effect of selected plant extracts on lipid accumulation in C. elegans. Currently no report could be found regarding lipid accumulation in C.elegans treated with ethanolic leaf extracts of jabon merah (Anthocephalus macrophyllus), jati belanda (Guazuma ulmifolia), and Mindi (Melia Azedarach) plants. Lipid accumulation was determined qualitatively using lipid staining method and quantitatively by colorimetry using sulpho-phospho-vanillin reagent. Data showed that lipid accumulation was inhibited up to 72% by extract of M. azedarach, about 35% by both of A. macrophyllus and G. ulmifolia extracts, and up to 25% by orlistat (a synthetic slimming drug). Ethanolic extract of A. macrophyllus, G. ulmifolia, and M. azedarach leaves were shown to inhibit lipid accumulation in C. elegans and M. azedarach leaves extracts was the most effective inhibitor. C.elegans were shown to be an effective model for in vivo lipid accumulation mechanism and potential to be used as a rapid screening assay for bioactive compounds with lipid accumulation inhibitory activity.

  5. Role of DAF-21protein in Caenorhabditis elegans immunity against Proteus mirabilis infection.

    Science.gov (United States)

    JebaMercy, Gnanasekaran; Durai, Sellegounder; Prithika, Udayakumar; Marudhupandiyan, Shanmugam; Dasauni, Pushpanjali; Kundu, Suman; Balamurugan, Krishnaswamy

    2016-08-11

    Caenorhabditis elegans is emerging as one of the handy model for proteome related studies due to its simplest system biology. The present study, deals with changes in protein expression in C. elegans infected with Proteus mirabilis. Proteins were separated using two-dimensional differential gel electrophoresis (2D-DIGE) and identified using MALDI-TOF. Twelve distinctly regulated proteins identified in the infected worms, included heat shock proteins involved stress pathway (HSP-1 and HSP-6), proteins involved in immune response pathway (DAF-21), enzymes involved in normal cellular process (Eukaryotic translation Elongation Factor, actin family member, S-adenosyl homocysteine hydrolase ortholog, glutamate dehydrogenase and Vacuolar H ATPase family member) and few least characterized proteins (H28O16.1 and H08J11.2). The regulation of selected players at the transcriptional level during Proteus mirabilis infection was analyzed using qPCR. Physiological experiments revealed the ability of P. mirabilis to kill daf-21 mutant C. elegans significantly compared with the wild type. This is the first report studying proteome changes in C. elegans and exploring the involvement of MAP Kinase pathway during P. mirabilis infection. This is the first report studying proteome changes in C. elegans during P. mirabilis infection. The present study explores the role and contribution of MAP Kinase pathway and its regulator protein DAF-21 involvement in the immunity against opportunistic pathogen P. mirabilis infection. Manipulation of this DAF-21 protein in host, may pave the way for new drug development or disease control strategy during opportunistic pathogen infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Feeding behaviour of Caenorhabditis elegans is an indicator of Pseudomonas aeruginosa PAO1 virulence

    Directory of Open Access Journals (Sweden)

    Shawn Lewenza

    2014-08-01

    Full Text Available Caenorhabditis elegans is commonly used as an infection model for pathogenesis studies in Pseudomonas aeruginosa. The standard virulence assays rely on the slow and fast killing or paralysis of nematodes but here we developed a behaviour assay to monitor the preferred bacterial food sources of C. elegans. We monitored the food preferences of nematodes fed the wild type PAO1 and mutants in the type III secretion (T3S system, which is a conserved mechanism to inject secreted effectors into the host cell cytosol. A ΔexsEΔpscD mutant defective for type III secretion served as a preferred food source, while an ΔexsE mutant that overexpresses the T3S effectors was avoided. Both food sources were ingested and observed in the gastrointestinal tract. Using the slow killing assay, we showed that the ΔexsEΔpscD had reduced virulence and thus confirmed that preferred food sources are less virulent than the wild type. Next we developed a high throughput feeding behaviour assay with 48 possible food colonies in order to screen a transposon mutant library and identify potential virulence genes. C. elegans identified and consumed preferred food colonies from a grid of 48 choices. The mutants identified as preferred food sources included known virulence genes, as well as novel genes not identified in previous C. elegans infection studies. Slow killing assays were performed and confirmed that several preferred food sources also showed reduced virulence. We propose that C. elegans feeding behaviour can be used as a sensitive indicator of virulence for P. aeruginosa PAO1.

  7. Effects of genetic mutations and chemical exposures on Caenorhabditis elegans feeding: evaluation of a novel, high-throughput screening assay.

    Directory of Open Access Journals (Sweden)

    Windy A Boyd

    2007-12-01

    Full Text Available Government agencies have defined a need to reduce, refine or replace current mammalian-based bioassays with testing methods that use alternative species. Invertebrate species, such as Caenorhabditis elegans, provide an attractive option because of their short life cycles, inexpensive maintenance, and high degree of evolutionary conservation with higher eukaryotes. The C. elegans pharynx is a favorable model for studying neuromuscular function, and the effects of chemicals on neuromuscular activity, i.e., feeding. Current feeding methodologies, however, are labor intensive and only semi-quantitative.Here a high-throughput assay is described that uses flow cytometry to measure C. elegans feeding by determining the size and intestinal fluorescence of hundreds of nematodes after exposure to fluorescent-labeled microspheres. This assay was validated by quantifying fluorescence in feeding-defective C. elegans (eat mutants, and by exposing wild-type nematodes to the neuroactive compounds, serotonin and arecoline. The eat mutations previously determined to cause slow pumping rates exhibited the lowest feeding levels with our assay. Concentration-dependent increases in feeding levels after serotonin exposures were dependent on food availability, while feeding levels decreased in arecoline-exposed nematodes regardless of the presence of food. The effects of the environmental contaminants, cadmium chloride and chlorpyrifos, on wild-type C. elegans feeding were then used to demonstrate an application of the feeding assay. Cadmium exposures above 200 microM led to a sharp drop in feeding levels. Feeding of chlorpyrifos-exposed nematodes decreased in a concentration-dependent fashion with an EC(50 of 2 microM.The C. elegans fluorescence microsphere feeding assay is a rapid, reliable method for the assessment of neurotoxic effects of pharmaceutical drugs, industrial chemicals or environmental agents. This assay may also be applicable to large scale genetic or

  8. Optical silencing of C. elegans cells with arch proton pump.

    Directory of Open Access Journals (Sweden)

    Ayako Okazaki

    Full Text Available BACKGROUND: Optogenetic techniques using light-driven ion channels or ion pumps for controlling excitable cells have greatly facilitated the investigation of nervous systems in vivo. A model organism, C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. METHODOLOGY/PRINCIPAL FINDINGS: We describe the application of archaerhodopsin-3 (Arch, a recently reported optical neuronal silencer, to C. elegans. Arch::GFP expressed either in all neurons or body wall muscles of the entire body by means of transgenes were localized, at least partially, to the cell membrane without adverse effects, and caused locomotory paralysis of worms when illuminated by green light (550 nm. Pan-neuronal expression of Arch endowed worms with quick and sustained responsiveness to such light. Worms reliably responded to repeated periods of illumination and non-illumination, and remained paralyzed under continuous illumination for 30 seconds. Worms expressing Arch in different subsets of motor neurons exhibited distinct defects in the locomotory behavior under green light: selective silencing of A-type motor neurons affected backward movement while silencing of B-type motor neurons affected forward movement more severely. Our experiments using a heat-shock-mediated induction system also indicate that Arch becomes fully functional only 12 hours after induction and remains functional for more than 24 hour. CONCLUSIONS/SGNIFICANCE: Arch can be used for silencing neurons and muscles, and may be a useful alternative to currently widely used halorhodopsin (NpHR in optogenetic studies of C. elegans.

  9. A microfluidic device for the continuous culture and analysis of Caenorhabditis elegans in a toxic aqueous environment

    Science.gov (United States)

    Jung, Jaehoon; Nakajima, Masahiro; Tajima, Hirotaka; Huang, Qiang; Fukuda, Toshio

    2013-08-01

    The nematode Caenorhabditis elegans (C. elegans) receives attention as a bioindicator, and the C. elegans condition has been recently analyzed using microfluidic devices equipped with an imaging system. To establish a method without an imaging system, we have proposed a novel microfluidic device with which to analyze the condition of C. elegans from the capacitance change using a pair of micro-electrodes. The device was designed to culture C. elegans, to expose C. elegans to an external stimulus, such as a chemical or toxicant, and to measure the capacitance change which indicates the condition of C. elegans. In this study, to demonstrate the capability of our device in a toxic aqueous environment, the device was applied to examine the effect of cadmium on C. elegans. Thirty L4 larval stage C. elegans were divided into three groups. One group was a control group and the other groups were exposed to cadmium solutions with concentrations of 5% and 10% LC50 for 24 h. The capacitance change and the body volume of C. elegans as a reference were measured four times and we confirmed the correlation between them. It shows that our device can analyze the condition of C. elegans without an imaging system.

  10. A microfluidic device for the continuous culture and analysis of Caenorhabditis elegans in a toxic aqueous environment

    International Nuclear Information System (INIS)

    Jung, Jaehoon; Tajima, Hirotaka; Fukuda, Toshio; Nakajima, Masahiro; Huang, Qiang

    2013-01-01

    The nematode Caenorhabditis elegans (C. elegans) receives attention as a bioindicator, and the C. elegans condition has been recently analyzed using microfluidic devices equipped with an imaging system. To establish a method without an imaging system, we have proposed a novel microfluidic device with which to analyze the condition of C. elegans from the capacitance change using a pair of micro-electrodes. The device was designed to culture C. elegans, to expose C. elegans to an external stimulus, such as a chemical or toxicant, and to measure the capacitance change which indicates the condition of C. elegans. In this study, to demonstrate the capability of our device in a toxic aqueous environment, the device was applied to examine the effect of cadmium on C. elegans. Thirty L4 larval stage C. elegans were divided into three groups. One group was a control group and the other groups were exposed to cadmium solutions with concentrations of 5% and 10% LC 50 for 24 h. The capacitance change and the body volume of C. elegans as a reference were measured four times and we confirmed the correlation between them. It shows that our device can analyze the condition of C. elegans without an imaging system. (paper)

  11. Toxicity-based toxicokinetic/toxicodynamic assessment of bioaccumulation and nanotoxicity of zerovalent iron nanoparticles in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Yang YF

    2017-06-01

    Full Text Available Ying-Fei Yang, Yi-Jun Lin, Chung-Min Liao Department of Bioenvironmental Systems Engineering, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan Abstract: Elucidating the relationships between the toxicity-based-toxicokinetic (TBTK/toxicodynamic (TD properties of engineered nanomaterials and their nanotoxicity is crucial for human health-risk analysis. Zerovalent iron (Fe0 nanoparticles (NPs are one of the most prominent NPs applied in remediating contaminated soils and groundwater. However, there are concerns that Fe0NP application contributes to long-term environmental and human health impacts. The nematode Caenorhabditis elegans is a surrogate in vivo model that has been successfully applied to assess the potential nanotoxicity of these nanomaterials. Here we present a TBTK/TD approach to appraise bioaccumulation and nanotoxicity of Fe0NPs in C. elegans. Built on a present C. elegans bioassay with estimated TBTK/TD parameters, we found that average bioconcentration factors in C. elegans exposed to waterborne and food-borne Fe0NPs were ~50 and ~5×10–3, respectively, whereas 10% inhibition concentrations for fertility, locomotion, and development, were 1.26 (95% CI 0.19–5.2, 3.84 (0.38–42, and 6.78 (2.58–21 µg·g–1, respectively, implicating that fertility is the most sensitive endpoint in C. elegans. Our results also showed that biomagnification effects were not observed in waterborne or food-borne Fe0NP-exposed worms. We suggest that the TBTK/TD assessment for predicting NP-induced toxicity at different concentrations and conditions in C. elegans could enable rapid selection of nanomaterials that are more likely to be nontoxic in larger animals. We conclude that the use of the TBTK/TD scheme manipulating C. elegans could be used for rapid evaluation of in vivo toxicity of NPs or for drug screening in the field of nanomedicine. Keywords: zerovalent iron nanoparticles, Caenorhabditis elegans

  12. The Alkaloid Compound Harmane Increases the Lifespan of Caenorhabditis elegans during Bacterial Infection, by Modulating the Nematode’s Innate Immune Response

    Science.gov (United States)

    Marinus, Martin G.; Xu, Tao; Struve, Carsten; Krogfelt, Karen A.; Løbner-Olesen, Anders

    2013-01-01

    The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes. We also found that the expression of the putative immune effector gene F35E12.5 was up-regulated in response to Harmane treatment. This indicates that Harmane stimulates the innate immune response of the nematode; thereby increasing its lifespan during bacterial infection. Expression of F35E12.5 is predominantly regulated through the p38 MAPK pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This indicates that Harmane has a complex effect on the innate immune system of C. elegans. Harmane could therefore be a useful tool in the further research into C. elegans immunity. Since the innate immunity of C. elegans has a high degree of evolutionary conservation, drugs such as Harmane could also be possible alternatives to classic antibiotics. The C. elegans model could prove to be useful for selection and development of such drugs. PMID:23544153

  13. Caenorhabditis elegans Egg-Laying Detection and Behavior Study Using Image Analysis

    Directory of Open Access Journals (Sweden)

    Palm Megan

    2005-01-01

    Full Text Available Egg laying is an important phase of the life cycle of the nematode Caenorhabditis elegans (C. elegans. Previous studies examined egg-laying events manually. This paper presents a method for automatic detection of egg-laying onset using deformable template matching and other morphological image analysis techniques. Some behavioral changes surrounding egg-laying events are also studied. The results demonstrate that the computer vision tools and the algorithm developed here can be effectively used to study C. elegans egg-laying behaviors. The algorithm developed is an essential part of a machine-vision system for C. elegans tracking and behavioral analysis.

  14. Worm Phenotype Ontology: Integrating phenotype data within and beyond the C. elegans community

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    Yook Karen

    2011-01-01

    Full Text Available Abstract Background Caenorhabditis elegans gene-based phenotype information dates back to the 1970's, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form. Results We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO. The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor. Conclusions We provide a phenotype ontology (WPO that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and

  15. Caenorhabditis elegans response to salt

    NARCIS (Netherlands)

    O.O. Umuerri (Oluwatoroti Omowayewa)

    2012-01-01

    textabstractThis thesis describes my work, where I used genetic methods to identify new genes involved in salt taste in C. elegans. In addition, I used calcium imaging to characterize the cellular response of C. elegans to salt. The thesis is divided into five sections and each section is summarized

  16. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

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    Zeng YX

    2016-04-01

    Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

  17. Combination of Metabolomic and Proteomic Analysis Revealed Different Features among Lactobacillus delbrueckii Subspecies bulgaricus and lactis Strains While In Vivo Testing in the Model Organism Caenorhabditis elegans Highlighted Probiotic Properties

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    Elena Zanni

    2017-06-01

    Full Text Available Lactobacillus delbrueckii represents a technologically relevant member of lactic acid bacteria, since the two subspecies bulgaricus and lactis are widely associated with fermented dairy products. In the present work, we report the characterization of two commercial strains belonging to L. delbrueckii subspecies bulgaricus, lactis and a novel strain previously isolated from a traditional fermented fresh cheese. A phenomic approach was performed by combining metabolomic and proteomic analysis of the three strains, which were subsequently supplemented as food source to the model organism Caenorhabditis elegans, with the final aim to evaluate their possible probiotic effects. Restriction analysis of 16S ribosomal DNA revealed that the novel foodborne strain belonged to L. delbrueckii subspecies lactis. Proteomic and metabolomic approaches showed differences in folate, aminoacid and sugar metabolic pathways among the three strains. Moreover, evaluation of C. elegans lifespan, larval development, brood size, and bacterial colonization capacity demonstrated that L. delbrueckii subsp. bulgaricus diet exerted beneficial effects on nematodes. On the other hand, both L. delbrueckii subsp. lactis strains affected lifespan and larval development. We have characterized three strains belonging to L. delbrueckii subspecies bulgaricus and lactis highlighting their divergent origin. In particular, the two closely related isolates L. delbrueckii subspecies lactis display different galactose metabolic capabilities. Moreover, the L. delbrueckii subspecies bulgaricus strain demonstrated potential probiotic features. Combination of omic platforms coupled with in vivo screening in the simple model organism C. elegans is a powerful tool to characterize industrially relevant bacterial isolates.

  18. Combination of Metabolomic and Proteomic Analysis Revealed Different Features among Lactobacillus delbrueckii Subspecies bulgaricus and lactis Strains While In Vivo Testing in the Model Organism Caenorhabditis elegans Highlighted Probiotic Properties.

    Science.gov (United States)

    Zanni, Elena; Schifano, Emily; Motta, Sara; Sciubba, Fabio; Palleschi, Claudio; Mauri, Pierluigi; Perozzi, Giuditta; Uccelletti, Daniela; Devirgiliis, Chiara; Miccheli, Alfredo

    2017-01-01

    Lactobacillus delbrueckii represents a technologically relevant member of lactic acid bacteria, since the two subspecies bulgaricus and lactis are widely associated with fermented dairy products. In the present work, we report the characterization of two commercial strains belonging to L. delbrueckii subspecies bulgaricus , lactis and a novel strain previously isolated from a traditional fermented fresh cheese. A phenomic approach was performed by combining metabolomic and proteomic analysis of the three strains, which were subsequently supplemented as food source to the model organism Caenorhabditis elegans , with the final aim to evaluate their possible probiotic effects. Restriction analysis of 16S ribosomal DNA revealed that the novel foodborne strain belonged to L. delbrueckii subspecies lactis . Proteomic and metabolomic approaches showed differences in folate, aminoacid and sugar metabolic pathways among the three strains. Moreover, evaluation of C. elegans lifespan, larval development, brood size, and bacterial colonization capacity demonstrated that L. delbrueckii subsp. bulgaricus diet exerted beneficial effects on nematodes. On the other hand, both L. delbrueckii subsp. lactis strains affected lifespan and larval development. We have characterized three strains belonging to L. delbrueckii subspecies bulgaricus and lactis highlighting their divergent origin. In particular, the two closely related isolates L. delbrueckii subspecies lactis display different galactose metabolic capabilities. Moreover, the L. delbrueckii subspecies bulgaricus strain demonstrated potential probiotic features. Combination of omic platforms coupled with in vivo screening in the simple model organism C. elegans is a powerful tool to characterize industrially relevant bacterial isolates.

  19. Physicochemical properties of the modeled structure of astacin metalloprotease moulting enzyme NAS-36 and mapping the druggable allosteric space of Heamonchus contortus, Brugia malayi and Ceanorhabditis elegans via molecular dynamics simulation.

    Science.gov (United States)

    Sharma, Om Prakash; Agrawal, Sonali; Kumar, M Suresh

    2013-12-01

    Nematodes represent the second largest phylum in the animal kingdom. It is the most abundant species (500,000) in the planet. It causes chronic, debilitating infections worldwide such as ascariasis, trichuriasis, hookworm, enterobiasis, strongyloidiasis, filariasis and trichinosis, among others. Molecular modeling tools can play an important role in the identification and structural investigation of molecular targets that can act as a vital candidate against filariasis. In this study, sequence analysis of NAS-36 from H. contortus (Heamonchus contortus), B. malayi (Brugia malayi) and C. elegans (Ceanorhabditis elegans) has been performed, in order to identify the conserved residues. Tertiary structure was developed for an insight into the molecular structure of the enzyme. Molecular Dynamics Simulation (MDS) studies have been carried out to analyze the stability and the physical properties of the proposed enzyme models in the H. contortus, B. malayi and C. elegans. Moreover, the drug binding sites have been mapped for inhibiting the function of NAS-36 enzyme. The molecular identity of this protease could eventually demonstrate how ex-sheathment is regulated, as well as provide a potential target of anthelmintics for the prevention of nematode infections.

  20. Study of multi-generational effects of a chronic exposure to ionizing radiations at a model organism: the nematode Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Buisset-Goussen, Adeline

    2014-01-01

    The environmental risk assessment of chronic exposure to ionizing radiation (natural and ubiquitous phenomenon enhanced by human activities) has become a major concern. Few studies relating to chronic exposure over several generations - essential knowledge to better understand the disruption caused by ionizing radiation and its possible consequences on the population - exist. In addition, it has become necessary to understand the mechanisms of disturbances related to ionizing radiation at the molecular and cellular level. Without this mechanistic understanding, it is difficult to extrapolate the effects observed between the different levels of biological organization and between different species. The aim of this PhD was to study the multi-generational effects of chronic gamma radiation in an integrated manner (to the life history traits from the subcellular mechanisms) in a model organism, the nematode Caenorhabditis elegans. A two-step strategy was implemented. First, studying the effects of chronic gamma radiation on the life history traits of C. elegans was performed. The objective of this experiment was to test the hypothesis of an increase of the sensitivity according generations. For that, three generations have been exposed to different dose rates. In parallel, two generations have been placed in 'control' environment after parental exposure to test a possible transmission of maternal effects. The second part of this thesis aimed to characterize the different subcellular mechanisms that could explain the observed effects on the life history traits after multi-generational exposure. The results showed that (i) the cumulative number of larvae was the most sensitive endpoint to gamma radiation, (ii) an increase in radiosensitivity was observed over three exposed generations and (iii) the effects of the parental generation were transmitted to the non-exposed generations. An increase in apoptosis, a reduction in the stock of sperm, and to a lesser

  1. Microbeam irradiation of the C. elegans nematode

    International Nuclear Information System (INIS)

    Bertucci, Antonella; Brenner, David J.; Pocock, Roger D.J.; Randers-Pehrson, Gerhard

    2009-01-01

    The understanding of complex radiation responses in biological systems, such as non-targeted effects as represented by the bystander response, can be enhanced by the use of genetically amenable model organisms. Almost all bystander studies to date have been carried out by using conventional single-cell in vitro systems, which are useful tools to characterize basic cellular and molecular responses. A few studies have been reported in monolayer explants and bystander responses have been also investigated in a three-dimensional normal human tissue system. However, despite the well-know usefulness of in vitro models, they cannot capture the complexity of radiation responses of living systems such as animal models. To carry out in vivo studies on the bystander effect we have developed a new technique to expose living organisms using proton microbeams. We report the use of a nematode C. elegans strain with a Green Fluorescent Protein (GFP) reporter for the hsp-4 heat-shock gene as an in vivo model for radiation studies. Exposing animals to heat and chemicals stressors leads to whole body increases in the hsp-4 protein reflected by enhanced fluorescence. We report here that γ-rays also can induce stress response in a dose dependent manner. However, whole body exposure to stress agents does not allow for evaluation of distance dependent response in non targeted tissues: the so-called bystander effect. We used the RARAF microbeam to site specifically deliver 3 MeV protons to a site in the tail of young worms. GFP expression was enhanced after 24 hours in a number dependent manner at distances > 100 μm from the site of irradiation. (author)

  2. Acute drug treatment in the early C. elegans embryo.

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    Ana Carvalho

    Full Text Available Genetic and genome-wide RNAi approaches available in C. elegans, combined with tools for visualizing subcellular events with high-resolution, have led to increasing adoption of the early C. elegans embryo as a model for mechanistic and functional genomic analysis of cellular processes. However, a limitation of this system has been the impermeability of the embryo eggshell, which has prevented the routine use of small molecule inhibitors. Here, we present a method to permeabilize and immobilize embryos for acute inhibitor treatment in conjunction with live imaging. To identify a means to permeabilize the eggshell, we used a dye uptake assay to screen a set of 310 candidate genes defined by a combination of bioinformatic criteria. This screen identified 20 genes whose inhibition resulted in >75% eggshell permeability, and 3 that permeabilized embryos with minimal deleterious effects on embryo production and early embryonic development. To mount permeabilized embryos for acute drug addition in conjunction with live imaging, we combined optimized inhibition of one of these genes with the use of a microfabricated chamber that we designed. We demonstrate that these two developments enable the temporally controlled introduction of inhibitors for mechanistic studies. This method should also open new avenues of investigation by allowing profiling and specificity-testing of inhibitors through comparison with genome-wide phenotypic datasets.

  3. SLO-1-channels of parasitic nematodes reconstitute locomotor behaviour and emodepside sensitivity in Caenorhabditis elegans slo-1 loss of function mutants.

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    Claudia Welz

    2011-04-01

    Full Text Available The calcium-gated potassium channel SLO-1 in Caenorhabditis elegans was recently identified as key component for action of emodepside, a new anthelmintic drug with broad spectrum activity. In this study we identified orthologues of slo-1 in Ancylostoma caninum, Cooperia oncophora, and Haemonchus contortus, all important parasitic nematodes in veterinary medicine. Furthermore, functional analyses of these slo-1 orthologues were performed using heterologous expression in C. elegans. We expressed A. caninum and C. oncophora slo-1 in the emodepside-resistant genetic background of the slo-1 loss-of-function mutant NM1968 slo-1(js379. Transformants expressing A. caninum slo-1 from C. elegans slo-1 promoter were highly susceptible (compared to the fully emodepside-resistant slo-1(js379 and showed no significant difference in their emodepside susceptibility compared to wild-type C. elegans (p = 0.831. Therefore, the SLO-1 channels of A. caninum and C. elegans appear to be completely functionally interchangeable in terms of emodepside sensitivity. Furthermore, we tested the ability of the 5' flanking regions of A. caninum and C. oncophora slo-1 to drive expression of SLO-1 in C. elegans and confirmed functionality of the putative promoters in this heterologous system. For all transgenic lines tested, expression of either native C. elegans slo-1 or the parasite-derived orthologue rescued emodepside sensitivity in slo-1(js379 and the locomotor phenotype of increased reversal frequency confirming the reconstitution of SLO-1 function in the locomotor circuits. A potent mammalian SLO-1 channel inhibitor, penitrem A, showed emodepside antagonising effects in A. caninum and C. elegans. The study combined the investigation of new anthelmintic targets from parasitic nematodes and experimental use of the respective target genes in C. elegans, therefore closing the gap between research approaches using model nematodes and those using target organisms

  4. Chemistry and the worm: Caenorhabditis elegans as a platform for integrating chemical and biological research.

    Science.gov (United States)

    Hulme, S Elizabeth; Whitesides, George M

    2011-05-16

    This Review discusses the potential usefulness of the worm Caenorhabditis elegans as a model organism for chemists interested in studying living systems. C. elegans, a 1 mm long roundworm, is a popular model organism in almost all areas of modern biology. The worm has several features that make it attractive for biology: it is small (1000 cells), transparent, and genetically tractable. Despite its simplicity, the worm exhibits complex phenotypes associated with multicellularity: the worm has differentiated cells and organs, it ages and has a well-defined lifespan, and it is capable of learning and remembering. This Review argues that the balance between simplicity and complexity in the worm will make it a useful tool in determining the relationship between molecular-scale phenomena and organism-level phenomena, such as aging, behavior, cognition, and disease. Following an introduction to worm biology, the Review provides examples of current research with C. elegans that is chemically relevant. It also describes tools-biological, chemical, and physical-that are available to researchers studying the worm. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Structural and functional evaluation of C. elegans filamins FLN-1 and FLN-2.

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    Christina R DeMaso

    Full Text Available Filamins are long, flexible, multi-domain proteins composed of an N-terminal actin-binding domain (ABD followed by multiple immunoglobulin-like repeats (IgFLN. They function to organize and maintain the actin cytoskeleton, to provide scaffolds for signaling components, and to act as mechanical force sensors. In this study, we used transcript sequencing and homology modeling to characterize the gene and protein structures of the C. elegans filamin orthologs fln-1 and fln-2. Our results reveal that C. elegans FLN-1 is well conserved at the sequence level to vertebrate filamins, particularly in the ABD and several key IgFLN repeats. Both FLN-1 and the more divergent FLN-2 colocalize with actin in vivo. FLN-2 is poorly conserved, with at least 23 IgFLN repeats interrupted by large regions that appear to be nematode-specific. Our results indicate that many of the key features of vertebrate filamins are preserved in C. elegans FLN-1 and FLN-2, and suggest the nematode may be a very useful model system for further study of filamin function.

  6. Carqueja (Baccharis trimera Protects against Oxidative Stress and β-Amyloid-Induced Toxicity in Caenorhabditis elegans

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    Franciny Aparecida Paiva

    2015-01-01

    Full Text Available Carqueja (Baccharis trimera is a native plant found throughout South America. Several studies have shown that Carqueja has antioxidant activity in vitro, as well as anti-inflammatory, antidiabetic, analgesic, antihepatotoxic, and antimutagenic properties. However, studies regarding its antioxidant potential in vivo are limited. In this study, we used Caenorhabditis elegans as a model to examine the antioxidant effects of a Carqueja hydroalcoholic extract (CHE on stress resistance and lifespan and to investigate whether CHE has a protective effect in a C. elegans model for Alzheimer's disease. Here, we show for the first time, using in vivo assays, that CHE treatment improved oxidative stress resistance by increasing survival rate and by reducing ROS levels under oxidative stress conditions independently of the stress-related signaling pathways (p38, JNK, and ERK and transcription factors (SKN-1/Nrf and DAF-16/Foxo tested here. CHE treatment also increased the defenses against β-amyloid toxicity in C. elegans, in part by increasing proteasome activity and the expression of two heat shock protein genes. Our findings suggest a potential neuroprotective use for Carqueja, supporting the idea that dietary antioxidants are a promising approach to boost the defensive systems against stress and neurodegeneration.

  7. Investigating the biological impacts of nanoengineered materials in Caenorhabditis elegans and in vitro

    Science.gov (United States)

    Contreras, Elizabeth Quevedo

    In nematode Caenorhabditis elegans, the chronic and multi-generational toxicological effects of commercially relevant engineered nanoparticles (ENPs), such as quantum dots (QDs) and silver (AgNP) caused significant changes in a number of physiological endpoints. The increased water-solubility of ENPs in commercial products, for example, makes them increasingly bioavailable to terrestrial organisms exposed to pollution and waste in the soil. Since 2008, attention to the toxicology of nanomaterials in C. elegans continues to grow. Quantitative data on multiple physiological endpoints paired with metal analysis show the uptake of QDs and AgNPs, and their effects on nematode fitness. First, C. elegans were exposed for four generations through feeding to amphiphilic polymer coated CdSe/ZnS (core-shell QDs), CdSe (core QDs), and different sizes of AgNPs. These ENPs were readily ingested. QDs were qualitatively imaged in the digestive tract using a fluorescence microscopy and their and AgNP uptake quantitatively measured using ICP-MS. Each generation was analyzed for changes in lifespan, reproduction, growth and motility using an automated computer vision system. Core-shell QDs had little impact on C. elegans due to its metal shell coating. In contrast, core QDs lacked a metal shell coating, which caused significant changes to nematode physiology. iii In the same way, at high concentrations of 100 ppm, AgNP caused the most adverse effect to lifespan and reproduction related to particle size, but its adverse effect to motility had no correlation to particle size. Using C. elegans as an animal model allowed for a better understanding of the negative impacts of ENPs than with cytotoxicity tests. Lastly, to test the toxicity of water-dispersed fullerene (nanoC60) using human dermal fibroblast cells, this thesis investigated a suite of assays and methods in order to establish a standard set of cytotoxicity tests. Ten assays and methods assessed nanoC60 samples of different

  8. FGT-1 is a mammalian GLUT2-like facilitative glucose transporter in Caenorhabditis elegans whose malfunction induces fat accumulation in intestinal cells.

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    Shun Kitaoka

    Full Text Available Caenorhabditis elegans (C. elegans is an attractive animal model for biological and biomedical research because it permits relatively easy genetic dissection of cellular pathways, including insulin/IGF-like signaling (IIS, that are conserved in mammalian cells. To explore C. elegans as a model system to study the regulation of the facilitative glucose transporter (GLUT, we have characterized the GLUT gene homologues in C. elegans: fgt-1, R09B5.11, C35A11.4, F53H8.3, F48E3.2, F13B12.2, Y61A9LA.1, K08F9.1 and Y37A1A.3. The exogenous expression of these gene products in Xenopus oocytes showed transport activity to unmetabolized glucose analogue 2-deoxy-D-glucose only in FGT-1. The FGT-1-mediated transport activity was inhibited by the specific GLUT inhibitor phloretin and exhibited a Michaelis constant (Km of 2.8 mM. Mannose, galactose, and fructose were able to inhibit FGT-1-mediated 2-deoxy-D-glucose uptake (P < 0.01, indicating that FGT-1 is also able to transport these hexose sugars. A GFP fusion protein of FGT-1 was observed only on the basolateral membrane of digestive tract epithelia in C. elegans, but not in other tissues. FGT-1::eGFP expression was observed from early embryonic stages. The knockdown or mutation of fgt-1 resulted in increased fat staining in both wild-type and daf-2 (mammalian insulin receptor homologue mutant animals. Other common phenotypes of IIS mutant animals, including dauer formation and brood size reduction, were not affected by fgt-1 knockdown in wild-type or daf-2 mutants. Our results indicated that in C. elegans, FGT-1 is mainly a mammalian GLUT2-like intestinal glucose transporter and is involved in lipid metabolism.

  9. A timecourse analysis of systemic and gonadal effects of temperature on sexual development of the red-eared slider turtle Trachemys scripta elegans.

    Science.gov (United States)

    Czerwinski, Michael; Natarajan, Anirudh; Barske, Lindsey; Looger, Loren L; Capel, Blanche

    2016-12-01

    Temperature dependent sex determination (TSD) is the process by which the environmental temperature experienced during embryogenesis influences the sex of an organism, as in the red-eared slider turtle Trachemys scripta elegans. In accord with current paradigms of vertebrate sex determination, temperature is believed to exert its effects on sexual development in T. scripta entirely within the middle third of development, when the gonad is forming. However, whether temperature regulates the transcriptome in T. scripta early embryos in a manner that could influence secondary sex characteristics or establish a pro-male or pro-female environment has not been investigated. In addition, apart from a handful of candidate genes, very little is known about potential similarities between the expression cascade during TSD and the genetic cascade that drives mammalian sex determination. Here, we conducted an unbiased transcriptome-wide analysis of the effects of male- and female-promoting temperatures on the turtle embryo prior to gonad formation, and on the gonad during the temperature sensitive period. We found sexually dimorphic expression reflecting differences in steroidogenic enzymes and brain development prior to gonad formation. Within the gonad, we mapped a cascade of differential expression similar to the genetic cascade established in mammals. Using a Hidden Markov Model based clustering approach, we identified groups of genes that show heterochronic shifts between M. musculus and T. scripta. We propose a model in which multiple factors influenced by temperature accumulate during early gonadogenesis, and converge on the antagonistic regulation of aromatase to canalize sex determination near the end of the temperature sensitive window of development. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Resveratrol effects on life span and fertility of caenorhabditis elegans subject to 60Co gamma ray irradiation

    International Nuclear Information System (INIS)

    Ye Kai; Ji Chenbo; Guo Xirong; Gu Guixiong

    2011-01-01

    Caennorhabditis elegans was used as experimental model to investigate radiation effect of resveratrol on caenorhabditis elegans irradiated by 60 Co γ ray. Treatment with resveratrol can increase average life span and spawning rate, improve the survival rate of eggs, and protect their mitochondrion function of caenorhabditis elegans exposure to 60 Co γ ray. The results indicate that resveratrol has radiation protection effects, which might be related to its action on ROS decrease and mitochondrial defend. (authors)

  11. Longevity and Stress Resistant Property of 6-Gingerol from Zingiber officinale Roscoe in Caenorhabditis elegans.

    Science.gov (United States)

    Lee, Eun Byeol; Kim, Jun Hyeong; An, Chang Wan; Kim, Yeong Jee; Noh, Yun Jeong; Kim, Su Jin; Kim, Ju-Eun; Shrestha, Abinash Chandra; Ham, Ha-Neul; Leem, Jae-Yoon; Jo, Hyung-Kwon; Kim, Dae-Sung; Moon, Kwang Hyun; Lee, Jeong Ho; Jeong, Kyung Ok; Kim, Dae Keun

    2018-03-14

    In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans ( C. elegans ) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans , and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.

  12. Tenebrio molitor Extracts Modulate the Response to Environmental Stressors and Extend Lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Won, Seong-Min; Cha, Hye-Uk; Yi, Sun Shin; Kim, Sung-Jo; Park, Sang-Kyu

    2016-09-08

    Tenebrio molitor are large insects and their larvae are consumed as food in many countries. The nutritional composition of T. molitor has been studied and contains high amounts of proteins, unsaturated fatty acids, and valuable minerals. However, the bioactivity of T. molitor has not been fully understood. We examined the effects of T. molitor extracts on resistance to oxidative stress and organism's lifespan using Caenorhabditis elegans as a model system. The response to heat shock and ultraviolet (UV) irradiation was monitored in vivo. The extracts from T. molitor showed significant effects on resistance to oxidative stress and UV irradiation and extend both mean and maximum lifespan of C. elegans. The number of progeny produced significantly increased in animals supplemented with T. molitor extracts. In addition, the expression of hsp-16.2 and sod-3 was markedly upregulated by supplementation with T. molitor extracts. These findings suggest that T. molitor extracts can increase response to stressors and extend lifespan by the induction of longevity assurance genes in C. elegans.

  13. In vivo imaging and toxicity assessments of fluorescent nanodiamonds in Caenorhabditis elegans.

    Science.gov (United States)

    Mohan, Nitin; Chen, Chao-Sheng; Hsieh, Hsiao-Han; Wu, Yi-Chun; Chang, Huan-Cheng

    2010-09-08

    Nanoscale carbon materials hold great promise for biotechnological and biomedical applications. Fluorescent nanodiamond (FND) is a recent new addition to members of the nanocarbon family. Here, we report long-term in vivo imaging of FNDs in Caenorhabditis elegans (C. elegans) and explore the nano-biointeractions between this novel nanomaterial and the model organism. FNDs are introduced into wild-type C. elegans by either feeding them with colloidal FND solution or microinjecting FND suspension into the gonads of the worms. On feeding, bare FNDs stay in the intestinal lumen, while FNDs conjugated with biomolecules (such as dextran and bovine serum albumin) are absorbed into the intestinal cells. On microinjection, FNDs are dispersed in the gonad and delivered to the embryos and eventually into the hatched larvae in the next generation. The toxicity assessments, performed by employing longevity and reproductive potential as physiological indicators and measuring stress responses with use of reporter genes, show that FNDs are stable and nontoxic and do not cause any detectable stress to the worms. The high brightness, excellent photostability, and nontoxic nature of the nanomaterial have enabled continuous imaging of the whole digestive system and tracking of the cellular and developmental processes of the living organism for several days.

  14. Effects of ionizing radiation on locomotory behavior and mechanosensation in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Suzuki, Michiyo; Sakashita, Tetsuya; Kikuchi, Masahiro; Ohba, Hirofumi; Hamada, Nobuyuki; Funayama, Tomoo; Fukamoto, Kana; Kobayashi, Yasuhiko; Yanase, Sumino; Higashitani, Atsushi; Tsuji, Toshio

    2009-01-01

    Locomotory behavior (motility) and mechanosensation are of vital importance in animals. We examined the effects of ionizing radiation (IR) on locomotory behavior and mechanosensation using a model organism, the nematode Caenorhabditis elegans. Bacterial mechanosensation in C. elegans induces the dopamine-mediated slowing of locomotion in the presence of bacteria (food), known as the basal slowing response. We previously reported an IR-induced reduction of locomotory rate in the absence of food. In the present study, we observed a similar IR-induced reduction of locomotory rate in the cat-2 mutant, which is defective in bacterial mechanosensation. The dose response pattern of the locomotory rate in the presence of food was relatively flat in wild-type animals, but not in cat-2 mutants. This suggests that the dopamine system, which is related to bacterial mechanosensation in C. elegans, might have a dominant effect on locomotory rate in the presence of food, which masks the effects of other stimuli. Moreover, we found that the behavioral responses of hydrogen peroxide-exposed wild-type animals are similar to those of IR-exposed animals. Our findings suggest that the IR-induced reduction of locomotory rate in the absence of food is mediated by a different pathway from that for bacterial mechanosensation, at least partially through IR-produced hydrogen peroxide. (author)

  15. Distinct roles of the RasGAP family proteins in C. elegans associative learning and memory.

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    Gyurkó, M Dávid; Csermely, Péter; Sőti, Csaba; Steták, Attila

    2015-10-15

    The Ras GTPase activating proteins (RasGAPs) are regulators of the conserved Ras/MAPK pathway. Various roles of some of the RasGAPs in learning and memory have been reported in different model systems, yet, there is no comprehensive study to characterize all gap genes in any organism. Here, using reverse genetics and neurobehavioural tests, we studied the role of all known genes of the rasgap family in C. elegans in associative learning and memory. We demonstrated that their proteins are implicated in different parts of the learning and memory processes. We show that gap-1 contribute redundantly with gap-3 to the chemosensation of volatile compounds, gap-1 plays a major role in associative learning, while gap-2 and gap-3 are predominantly required for short- and long-term associative memory. Our results also suggest that the C. elegans Ras orthologue let-60 is involved in multiple processes during learning and memory. Thus, we show that the different classes of RasGAP proteins are all involved in cognitive function and their complex interplay ensures the proper formation and storage of novel information in C. elegans.

  16. Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans

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    Portal-Celhay Cynthia

    2012-03-01

    Full Text Available Abstract Background A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. Results We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. Conclusions In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.

  17. Stable nuclear transformation of Eudorina elegans

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    Lerche Kai

    2013-02-01

    Full Text Available Abstract Background A fundamental step in evolution was the transition from unicellular to differentiated, multicellular organisms. Volvocine algae have been used for several decades as a model lineage to investigate the evolutionary aspects of multicellularity and cellular differentiation. There are two well-studied volvocine species, a unicellular alga (Chlamydomonas reinhardtii and a multicellular alga with differentiated cell types (Volvox carteri. Species with intermediate characteristics also exist, which blur the boundaries between unicellularity and differentiated multicellularity. These species include the globular alga Eudorina elegans, which is composed of 16–32 cells. However, detailed molecular analyses of E. elegans require genetic manipulation. Unfortunately, genetic engineering has not yet been established for Eudorina, and only limited DNA and/or protein sequence information is available. Results Here, we describe the stable nuclear transformation of E. elegans by particle bombardment using both a chimeric selectable marker and reporter genes from different heterologous sources. Transgenic algae resistant to paromomycin were achieved using the aminoglycoside 3′-phosphotransferase VIII (aphVIII gene of Streptomyces rimosus, an actinobacterium, under the control of an artificial promoter consisting of two V. carteri promoters in tandem. Transformants exhibited an increase in resistance to paromomycin by up to 333-fold. Co-transformation with non-selectable plasmids was achieved with a rate of 50 - 100%. The luciferase (gluc gene from the marine copepod Gaussia princeps, which previously was engineered to match the codon usage of C. reinhardtii, was used as a reporter gene. The expression of gluc was mediated by promoters from C. reinhardtii and V. carteri. Heterologous heat shock promoters induced an increase in luciferase activity (up to 600-fold at elevated temperatures. Long-term stability and both constitutive and

  18. Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans

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    Sinha Amit

    2012-06-01

    Full Text Available Abstract Background An organism can respond to changing environmental conditions by adjusting gene regulation and by forming alternative phenotypes. In nematodes, these mechanisms are coupled because many species will form dauer larvae, a stress-resistant and non-aging developmental stage, when exposed to unfavorable environmental conditions, and execute gene expression programs that have been selected for the survival of the animal in the wild. These dauer larvae represent an environmentally induced, homologous developmental stage across many nematode species, sharing conserved morphological and physiological properties. Hence it can be expected that some core components of the associated transcriptional program would be conserved across species, while others might diverge over the course of evolution. However, transcriptional and metabolic analysis of dauer development has been largely restricted to Caenorhabditis elegans. Here, we use a transcriptomic approach to compare the dauer stage in the evolutionary model system Pristionchus pacificus with the dauer stage in C. elegans. Results We have employed Agilent microarrays, which represent 20,446 P. pacificus and 20,143 C. elegans genes to show an unexpected divergence in the expression profiles of these two nematodes in dauer and dauer exit samples. P. pacificus and C. elegans differ in the dynamics and function of genes that are differentially expressed. We find that only a small number of orthologous gene pairs show similar expression pattern in the dauers of the two species, while the non-orthologous fraction of genes is a major contributor to the active transcriptome in dauers. Interestingly, many of the genes acquired by horizontal gene transfer and orphan genes in P. pacificus, are differentially expressed suggesting that these genes are of evolutionary and functional importance. Conclusion Our data set provides a catalog for future functional investigations and indicates novel insight

  19. A method for measuring fatty acid oxidation in C. elegans

    DEFF Research Database (Denmark)

    Elle, Ida Coordt; Rødkær, Steven Vestergaard; Fredens, Julius

    2012-01-01

    The nematode C. elegans has during the past decade proven to be a valuable model organism to identify and examine molecular mechanisms regulating lipid storage and metabolism. While the primary approach has been to identify genes and pathways conferring alterations in lipid accumulation, only a few...... recent studies have recognized the central role of fatty acid degradation in cellular lipid homeostasis. In the present study, we show how complete oxidation of fatty acids can be determined in live C. elegans by examining oxidation of tritium-labeled fatty acids to tritiated H2O that can be measured......, the present methodology can be used to delineate the role of specific genes and pathways in the regulation of β-oxidation in C. elegans....

  20. Isolating genes involved with genotoxic drug response in the nematode Caenorhabditis elegans using genome-wide RNAi screening

    DEFF Research Database (Denmark)

    Schøler, Lone Vedel; Møller, Tine Hørning; Nørgaard, Steffen

    2012-01-01

    The soil nematode Caenorhabditis elegans has become a popular genetic model organism used to study a broad range of complex biological processes, including development, aging, apoptosis, and DNA damage responses. Many genetic tools and tricks have been developed in C. elegans including knock down...... of gene expression via RNA interference (RNAi). In C. elegans RNAi can effectively be administrated via feeding the nematodes bacteria expressing double-stranded RNA targeting the gene of interest. Several commercial C. elegans RNAi libraries are available and hence gene inactivation using RNAi can...

  1. Measuring Food Intake and Nutrient Absorption in Caenorhabditis elegans.

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    Gomez-Amaro, Rafael L; Valentine, Elizabeth R; Carretero, Maria; LeBoeuf, Sarah E; Rangaraju, Sunitha; Broaddus, Caroline D; Solis, Gregory M; Williamson, James R; Petrascheck, Michael

    2015-06-01

    Caenorhabditis elegans has emerged as a powerful model to study the genetics of feeding, food-related behaviors, and metabolism. Despite the many advantages of C. elegans as a model organism, direct measurement of its bacterial food intake remains challenging. Here, we describe two complementary methods that measure the food intake of C. elegans. The first method is a microtiter plate-based bacterial clearing assay that measures food intake by quantifying the change in the optical density of bacteria over time. The second method, termed pulse feeding, measures the absorption of food by tracking de novo protein synthesis using a novel metabolic pulse-labeling strategy. Using the bacterial clearance assay, we compare the bacterial food intake of various C. elegans strains and show that long-lived eat mutants eat substantially more than previous estimates. To demonstrate the applicability of the pulse-feeding assay, we compare the assimilation of food for two C. elegans strains in response to serotonin. We show that serotonin-increased feeding leads to increased protein synthesis in a SER-7-dependent manner, including proteins known to promote aging. Protein content in the food has recently emerged as critical factor in determining how food composition affects aging and health. The pulse-feeding assay, by measuring de novo protein synthesis, represents an ideal method to unequivocally establish how the composition of food dictates protein synthesis. In combination, these two assays provide new and powerful tools for C. elegans research to investigate feeding and how food intake affects the proteome and thus the physiology and health of an organism. Copyright © 2015 by the Genetics Society of America.

  2. Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses.

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    Jakob Begun

    2007-04-01

    Full Text Available Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms. The ability of staphylococci to produce biofilm is an important virulence mechanism that allows bacteria both to adhere to living and artificial surfaces and to resist host immune factors and antibiotics. Here, we show that the icaADBC locus, which synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA in staphylococci, is required for the formation of a lethal S. epidermidis infection in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38 mitogen-activated protein (MAP kinase or DAF-2 insulin-signaling pathways. Loss of PIA production abrogates nematocidal activity and leads to reduced bacterial accumulation in the C. elegans intestine, while overexpression of the icaADBC locus in S. aureus augments virulence towards nematodes. PIA-producing S. epidermidis has a significant survival advantage over ica-deficient S. epidermidis within the intestinal tract of wild-type C. elegans, but not in immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally sensitive to wild-type and icaADBC-deficient S. epidermidis. These results suggest that biofilm exopolysaccharide enhances virulence by playing an immunoprotective role during colonization of the C. elegans intestine. These studies demonstrate that C. elegans can serve as a simple animal model for studying host-pathogen interactions involving staphylococcal biofilm exopolysaccharide and suggest that the protective activity of biofilm matrix represents an ancient conserved function for resisting predation.

  3. Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates.

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    Irazoqui, Javier E; Urbach, Jonathan M; Ausubel, Frederick M

    2010-01-01

    The genetically tractable model organism Caenorhabditis elegans was first used to model bacterial virulence in vivo a decade ago. Since then, great strides have been made in identifying the host response pathways that are involved in its defence against infection. Strikingly, C. elegans seems to detect, and respond to, infection without the involvement of its homologue of Toll-like receptors, in contrast to the well-established role for these proteins in innate immunity in mammals. What, therefore, do we know about host defence mechanisms in C. elegans and what can they tell us about innate immunity in higher organisms?

  4. Evolution of host innate defence: insights from C. elegans and primitive invertebrates

    Science.gov (United States)

    Irazoqui, Javier E.; Urbach, Jonathan M.; Ausubel, Frederick M.

    2010-01-01

    Preface The genetically tractable model organism Caenorhabditis elegans was first used to model bacterial virulence in vivo a decade ago. Since then, great strides have been made in the identification of host response pathways that are involved in the defence against infection. Strikingly, C. elegans seems to detect and respond to infection without the involvement of its Toll-like receptor homologue, in contrast to the well-established role for these proteins in innate immunity in mammals. What, therefore, do we know about host defence mechanisms in C. elegans, and what can they tell us about innate immunity in higher organisms? PMID:20029447

  5. Lack of the RNA chaperone Hfq attenuates pathogenicity of several Escherichia coli pathotypes towards Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Bojer, Martin Saxtorph; Jakobsen, Henrik; Struve, Carsten

    2012-01-01

    as a model for virulence characterization and screening for novel antimicrobial entities. Several E. coli human pathotypes are also pathogenic towards C. elegans, and we show here that lack of the RNA chaperone Hfq significantly reduces pathogenicity of VTEC, EAEC, and UPEC in the nematode model. Thus, Hfq...... is intrinsically essential to pathogenic E. coli for survival and virulence exerted in the C. elegans host.......Escherichia coli is an important agent of Gram-negative bacterial infections worldwide, being one of the leading causes of diarrhoea and urinary tract infections. Strategies to understand pathogenesis and develop therapeutic compounds include the use of the nematode Caenorhabditis elegans...

  6. In Vivo Modelling of ATP1A3 G316S-Induced Ataxia in C. elegans Using CRISPR/Cas9-Mediated Homologous Recombination Reveals Dominant Loss of Function Defects.

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    Altar Sorkaç

    Full Text Available The NIH Undiagnosed Diseases Program admitted a male patient with unclassifiable late-onset ataxia-like symptoms. Exome sequencing revealed a heterozygous de novo mutation converting glycine 316 to serine in ATP1A3, which might cause disease. ATP1A3 encodes the Na+/K+ ATPase pump α3-subunit. Using CRISPR/Cas9-mediated homologous recombination for genome editing, we modelled this putative disease-causing allele in Caenorhabditis elegans, recreating the patient amino acid change in eat-6, the orthologue of ATP1A3. The impact of the mutation on eat-6 function at the neuromuscular junction was examined using two behavioural assays: rate of pharyngeal pumping and sensitivity to aldicarb, a drug that causes paralysis over time via the inhibition of acetylcholinesterase. The patient allele decreased pumping rates and caused hypersensitivity to aldicarb. Animals heterozygous for the allele exhibited similar defects, whereas loss of function mutations in eat-6 were recessive. These results indicate that the mutation is dominant and impairs the neuromuscular function. Thus, we conclude that the de novo G316S mutation in ATP1A3 likely causes or contributes to patient symptoms. More broadly, we conclude that, for conserved genes, it is possible to rapidly and easily model human diseases in C. elegans using CRIPSR/Cas9 genome editing.

  7. Formation of longitudinal axon pathways in Caenorhabditis elegans.

    Science.gov (United States)

    Hutter, Harald

    2017-11-18

    The small number of neurons and the simple architecture of the Caenorhabditis elegans (C. elegans) nervous system enables researchers to study axonal pathfinding at the level of individually identified axons. Axons in C. elegans extend predominantly along one of the two major body axes, the anterior-posterior axis and the dorso-ventral axis. This review will focus on axon navigation along the anterior-posterior axis, leading to the establishment of the longitudinal axon tracts, with a focus on the largest longitudinal axon tract, the ventral nerve cord (VNC). In the VNC, axons grow out in a stereotypic order, with early outgrowing axons (pioneers) playing an important role in guiding later outgrowing (follower) axons. Genetic screens have identified a number of genes specifically affecting the formation of longitudinal axon tracts. These genes include secreted proteins, putative receptors and adhesion molecules, as well as intracellular proteins regulating the cell's response to guidance cues. In contrast to dorso-ventral navigation, no major general guidance cues required for the establishment of longitudinal pathways have been identified so far. The limited penetrance of defects found in many mutants affecting longitudinal navigation suggests that guidance cues act redundantly in this process. The majority of the axon guidance genes identified in C. elegans are evolutionary conserved, i.e. have homologs in other animals, including vertebrates. For a number of these genes, a role in axon guidance has not been described outside C. elegans. Taken together, studies in C. elegans contribute to a fundamental understanding of the molecular basis of axonal navigation that can be extended to other animals, including vertebrates and probably humans as well. Copyright © 2017. Published by Elsevier Ltd.

  8. C. elegans microRNAs.

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    Vella, Monica C; Slack, Frank J

    2005-09-21

    MicroRNAs (miRNAs) are small, non-coding regulatory RNAs found in many phyla that control such diverse events as development, metabolism, cell fate and cell death. They have also been implicated in human cancers. The C. elegans genome encodes hundreds of miRNAs, including the founding members of the miRNA family lin-4 and let-7. Despite the abundance of C. elegans miRNAs, few miRNA targets are known and little is known about the mechanism by which they function. However, C. elegans research continues to push the boundaries of discovery in this area. lin-4 and let-7 are the best understood miRNAs. They control the timing of adult cell fate determination in hypodermal cells by binding to partially complementary sites in the mRNA of key developmental regulators to repress protein expression. For example, lin-4 is predicted to bind to seven sites in the lin-14 3' untranslated region (UTR) to repress LIN-14, while let-7 is predicted to bind two let-7 complementary sites in the lin-41 3' UTR to down-regulate LIN-41. Two other miRNAs, lsy-6 and mir-273, control left-right asymmetry in neural development, and also target key developmental regulators for repression. Approximately one third of the C. elegans miRNAs are differentially expressed during development indicating a major role for miRNAs in C. elegans development. Given the remarkable conservation of developmental mechanism across phylogeny, many of the principles of miRNAs discovered in C. elegans are likely to be applicable to higher animals.

  9. Automated high-content live animal drug screening using C. elegans expressing the aggregation prone serpin α1-antitrypsin Z.

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    Sager J Gosai

    2010-11-01

    Full Text Available The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms.

  10. Analyzing modifiers of protein aggregation in C. elegans by native agarose gel electrophoresis

    NARCIS (Netherlands)

    Holmberg, Mats; Nollen, Ellen A A; Hatters, Danny M.; Hannan, Anthony J.

    2013-01-01

    The accumulation of specific aggregation-prone proteins during aging is thought to be involved in several diseases, most notably Alzheimer's and Parkinson's disease as well as polyglutamine expansion disorders such as Huntington's disease. Caenorhabditis elegans disease models with transgenic

  11. Lifespan decrease in a Caenorhabditis elegans mutant lacking TRX-1, a thioredoxin expressed in ASJ sensory neurons.

    Science.gov (United States)

    Miranda-Vizuete, Antonio; Fierro González, Juan Carlos; Gahmon, Gabriele; Burghoorn, Jan; Navas, Plácido; Swoboda, Peter

    2006-01-23

    Thioredoxins are a class of small proteins that play a key role in regulating many cellular redox processes. We report here the characterization of the first member of the thioredoxin family in metazoans that is mainly associated with neurons. The Caenorhabditis elegans gene B0228.5 encodes a thioredoxin (TRX-1) that is expressed in ASJ ciliated sensory neurons, and to some extent also in the posterior-most intestinal cells. TRX-1 is active at reducing protein disulfides in the presence of a heterologous thioredoxin reductase. A mutant worm strain carrying a null allele of the trx-1 gene displays a reproducible decrease in both mean and maximum lifespan when compared to wild-type. The identification and characterization of TRX-1 paves the way to use C. elegans as an in vivo model to study the role of thioredoxins in lifespan and nervous system physiology and pathology.

  12. Nanoscale mechanical stimulation method for quantifying C. elegans mechanosensory behavior and memory

    OpenAIRE

    Kiso, Kaori; Sugi, Takuma; Okumura, Etsuko; Igarashi, Ryuji

    2016-01-01

    Here, we establish a novel economic system to quantify C. elegans mechanosensory behavior and memory by a controllable nanoscale mechanical stimulation. Using piezoelectric sheet speaker, we can flexibly change the vibration properties at a nanoscale displacement level and quantify behavioral responses and memory under the control of each vibration property. This system will facilitate understanding of physiological aspects of C. elegans mechanosensory behavior and memory.

  13. Evaluation of pesticide toxicities with differing mechanisms using Caenorhabditis elegans.

    Science.gov (United States)

    Ruan, Qin-Li; Ju, Jing-Juan; Li, Yun-Hui; Liu, Ran; Pu, Yue-Pu; Yin, Li-Hong; Wang, Da-Yong

    2009-01-01

    The aim of this study was to (1) determine whether model organism Caenorhabditis elegans was sensitive to pesticides at the maximum concentration limits regulated by national agency standards, and (2) examine the multi-biological toxicities occurring as a result of exposure to pesticides. Five pesticides, namely, chlorpyrifos, imibacloprid, buprofezin, cyhalothrin, and glyphosate, with four different mechanisms of action were selected for the investigation. In accordance with national agency requirements, 4 exposed groups were used for each tested pesticide with the concentration scales ranging from 1.0 x 10(-3) to 1 mg/L. L4 larvae were exposed for 24 and 72 h, respectively. Endpoints of locomotion, propagation, and development were selected for the assay as parameters of toxicity. After exposure for 24 h, both the body bend frequency and head thrash frequency of nematodes exposed to chlorpyrifos, imibacloprid, and cyhalothrin decreased in a concentration-dependent manner, and there were significant differences between exposed groups at maximum concentration level (MCL) compared to control. The generation time of nematodes exposed to buprofezin 24 h significantly increased in a concentration-dependent manner in the highest exposed group. When exposed for 72 h, the body bend frequency and head thrash frequency of nematodes exposed to cyhalothrin markedly decreased at MCL. The generation time and brood size of nematodes exposed to buprofezin were reduced in a concentration-dependent manner. The behavior of nematodes was sensitive to pesticides with neurotoxic properties, while pesticides affecting insect growth modified the reproductive system. The effects of pesticides on nematodes exposed for 24 h appeared more sensitive than with exposure for 72 h. Caenorhabditis elegans may thus be used for assessing the adverse effects of pesticide residues in aquatic environment.

  14. Precision Electrophile Tagging in Caenorhabditis elegans.

    Science.gov (United States)

    Long, Marcus J C; Urul, Daniel A; Chawla, Shivansh; Lin, Hong-Yu; Zhao, Yi; Haegele, Joseph A; Wang, Yiran; Aye, Yimon

    2018-01-16

    Adduction of an electrophile to privileged sensor proteins and the resulting phenotypically dominant responses are increasingly appreciated as being essential for metazoan health. Functional similarities between the biological electrophiles and electrophilic pharmacophores commonly found in covalent drugs further fortify the translational relevance of these small-molecule signals. Genetically encodable or small-molecule-based fluorescent reporters and redox proteomics have revolutionized the observation and profiling of cellular redox states and electrophile-sensor proteins, respectively. However, precision mapping between specific redox-modified targets and specific responses has only recently begun to be addressed, and systems tractable to both genetic manipulation and on-target redox signaling in vivo remain largely limited. Here we engineer transgenic Caenorhabditis elegans expressing functional HaloTagged fusion proteins and use this system to develop a generalizable light-controlled approach to tagging a prototypical electrophile-sensor protein with native electrophiles in vivo. The method circumvents issues associated with low uptake/distribution and toxicity/promiscuity. Given the validated success of C. elegans in aging studies, this optimized platform offers a new lens with which to scrutinize how on-target electrophile signaling influences redox-dependent life span regulation.

  15. Role of protein kinase C β and vascular endothelial growth factor receptor in malignant pleural mesothelioma: Therapeutic implications and the usefulness of Caenorhabditis elegans model organism

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    Sivakumar Loganathan

    2011-01-01

    Full Text Available Purpose: To examine the role of both protein kinase C (PKC-β and vascular endothelial growth factor receptor (VEGFR-2 in malignant pleural mesothelioma (MPM using respective inhibitors, enzastaurin and KRN633. Materials and Methods: MPM cell lines, control cells, and a variety of archived MPM tumor samples were used to determine the protein expression levels of PKC-β, VEGFR-2, VEGF, and p-AKT. Effects of enzastaurin and KRN633 on phosphorylation status of key signaling molecules and viability of the mesothelioma cells were determined. The common soil nematode, Caenorhabditis elegans, was treated with enzastaurin to determine its suitability to screen for highly potent kinase inhibitors. Results: PKC-β1, PKC-β2 and VEGFR-2/KDR were overexpressed in MPM cell lines and MPM tumor tissues. Enzastaurin treatment resulted in significant loss in viability of VEGF induced cell proliferation; however, the effect of KRN633 was much less. Enzastaurin also dramatically decreased the phosphorylation of PKC-β, its downstream target p-AKT, and surprisingly, the upstream VEGFR-2. The combination of the two drugs at best was additive and similar results were obtained with respect to cell viability. Treatment of C. elegans with enzastaurin resulted in clear phenotypic changes and the worms were hypermotile with abnormal pattern and shape of eggs, suggesting altered fecundity. Conclusions: PKC-β1 and VEGFR-2 are both excellent therapeutic targets in MPM. Enzastaurin was better at killing MPM cells than KRN633 and the combination lacked synergy. In addition, we show here that C. elegans can be used to screen for the next generation inhibitors as treatment with enzastaurin resulted in clear phenotypic changes that could be assayed.

  16. Population dynamics and habitat sharing of natural populations of Caenorhabditis elegans and C. briggsae

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    Félix Marie-Anne

    2012-06-01

    Full Text Available Abstract Background The nematode Caenorhabditis elegans is a major model organism in laboratory biology. Very little is known, however, about its ecology, including where it proliferates. In the past, C. elegans was mainly isolated from human-made compost heaps, where it was overwhelmingly found in the non-feeding dauer diapause stage. Results C. elegans and C. briggsae were found in large, proliferating populations in rotting plant material (fruits and stems in several locations in mainland France. Both species were found to co-occur in samples isolated from a given plant species. Population counts spanned a range from one to more than 10,000 Caenorhabditis individuals on a single fruit or stem. Some populations with an intermediate census size (10 to 1,000 contained no dauer larvae at all, whereas larger populations always included some larvae in the pre-dauer or dauer stages. We report on associated micro-organisms, including pathogens. We systematically sampled a spatio-temporally structured set of rotting apples in an apple orchard in Orsay over four years. C. elegans and C. briggsae were abundantly found every year, but their temporal distributions did not coincide. C. briggsae was found alone in summer, whereas both species co-occurred in early fall and C. elegans was found alone in late fall. Competition experiments in the laboratory at different temperatures show that C. briggsae out-competes C. elegans at high temperatures, whereas C. elegans out-competes C. briggsae at lower temperatures. Conclusions C. elegans and C. briggsae proliferate in the same rotting vegetal substrates. In contrast to previous surveys of populations in compost heaps, we found fully proliferating populations with no dauer larvae. The temporal sharing of the habitat by the two species coincides with their temperature preference in the laboratory, with C. briggsae populations growing faster than C. elegans at higher temperatures, and vice at lower temperatures.

  17. The Effect of Vitamin E on the Survival Rate of unc-13 Caenorhabditis elegans mutants under Oxidative Stress

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    Jessica Porcelan

    2012-01-01

    Full Text Available Caenorhabditis elegans unc-13 mutants express decreased neuronal activity and thus are a good model strain for examining defective nervous systems. These unc-13 mutants as well as wild type N2 strains, show rapid mortality when under oxidative stress. However, the antioxidant vitamin E may prolong survival in unc-13 mutant and N2 strains under oxidative stress. The addition of vitamin E to organisms under oxidative stress has a protective effect in both N2 and unc-13 C. elegans strains. Interestingly, vitamin E resulted in a greater increase in survival rate in N2 worms than with unc-13 mutant worms. While both strains displayed lower mortality rates with the addition of vitamin E, this finding suggests that vitamin E more efficiently increases survival rates of C. elegans with typical nervous system function. The efficacy of vitamin E implies that use of antioxidants may lessen the damage caused by oxidative stress in both N2 and mutant worms.

  18. Synaptic Vesicle Endocytosis in Different Model Systems

    Directory of Open Access Journals (Sweden)

    Quan Gan

    2018-06-01

    Full Text Available Neurotransmission in complex animals depends on a choir of functionally distinct synapses releasing neurotransmitters in a highly coordinated manner. During synaptic signaling, vesicles fuse with the plasma membrane to release their contents. The rate of vesicle fusion is high and can exceed the rate at which synaptic vesicles can be re-supplied by distant sources. Thus, local compensatory endocytosis is needed to replenish the synaptic vesicle pools. Over the last four decades, various experimental methods and model systems have been used to study the cellular and molecular mechanisms underlying synaptic vesicle cycle. Clathrin-mediated endocytosis is thought to be the predominant mechanism for synaptic vesicle recycling. However, recent studies suggest significant contribution from other modes of endocytosis, including fast compensatory endocytosis, activity-dependent bulk endocytosis, ultrafast endocytosis, as well as kiss-and-run. Currently, it is not clear whether a universal model of vesicle recycling exist for all types of synapses. It is possible that each synapse type employs a particular mode of endocytosis. Alternatively, multiple modes of endocytosis operate at the same synapse, and the synapse toggles between different modes depending on its activity level. Here we compile review and research articles based on well-characterized model systems: frog neuromuscular junctions, C. elegans neuromuscular junctions, Drosophila neuromuscular junctions, lamprey reticulospinal giant axons, goldfish retinal ribbon synapses, the calyx of Held, and rodent hippocampal synapses. We will compare these systems in terms of their known modes and kinetics of synaptic vesicle endocytosis, as well as the underlying molecular machineries. We will also provide the future development of this field.

  19. Neuronal and non-neuronal signals regulate Caernorhabditis elegans avoidance of contaminated food.

    Science.gov (United States)

    Anderson, Alexandra; McMullan, Rachel

    2018-07-19

    One way in which animals minimize the risk of infection is to reduce their contact with contaminated food. Here, we establish a model of pathogen-contaminated food avoidance using the nematode worm Caernorhabditis elegans We find that avoidance of pathogen-contaminated food protects C. elegans from the deleterious effects of infection and, using genetic approaches, demonstrate that multiple sensory neurons are required for this avoidance behaviour. In addition, our results reveal that the avoidance of contaminated food requires bacterial adherence to non-neuronal cells in the tail of C. elegans that are also required for the cellular immune response. Previous studies in C. elegans have contributed significantly to our understanding of molecular and cellular basis of host-pathogen interactions and our model provides a unique opportunity to gain basic insights into how animals avoid contaminated food.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'. © 2018 The Authors.

  20. Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    John T Murphy

    2011-03-01

    Full Text Available Zinc is an essential trace element involved in a wide range of biological processes and human diseases. Zinc excess is deleterious, and animals require mechanisms to protect against zinc toxicity. To identify genes that modulate zinc tolerance, we performed a forward genetic screen for Caenorhabditis elegans mutants that were resistant to zinc toxicity. Here we demonstrate that mutations of the C. elegans histidine ammonia lyase (haly-1 gene promote zinc tolerance. C. elegans haly-1 encodes a protein that is homologous to vertebrate HAL, an enzyme that converts histidine to urocanic acid. haly-1 mutant animals displayed elevated levels of histidine, indicating that C. elegans HALY-1 protein is an enzyme involved in histidine catabolism. These results suggest the model that elevated histidine chelates zinc and thereby reduces zinc toxicity. Supporting this hypothesis, we demonstrated that dietary histidine promotes zinc tolerance. Nickel is another metal that binds histidine with high affinity. We demonstrated that haly-1 mutant animals are resistant to nickel toxicity and dietary histidine promotes nickel tolerance in wild-type animals. These studies identify a novel role for haly-1 and histidine in zinc metabolism and may be relevant for other animals.

  1. Biophysical and biological meanings of healthspan from C. elegans cohort

    International Nuclear Information System (INIS)

    Suda, Hitoshi

    2014-01-01

    Highlights: • We focus on a third factor, noise, as well as on genetic and environmental factors. • C. elegans fed a healthy food had an extended healthspan as compared to those fed a conventional diet. • An amplification of ATP noise was clearly evident from around the onset of biodemographic aging. • The extension of timing of noise amplification may contribute to effectively extending the healthspan. • The same mechanism of the mean lifespan extension in C. elegans may be realized in humans. - Abstract: Lifespan among individuals ranges widely in organisms from yeast to mammals, even in an isogenic cohort born in a nearly uniform environment. Needless to say, genetic and environmental factors are essential for aging and lifespan, but in addition, a third factor or the existence of a stochastic element must be reflected in aging and lifespan. An essential point is that lifespan or aging is an unpredictable phenomenon. The present study focuses on elucidating the biophysical and biological meanings of healthspan that latently indwells a stochastic nature. To perform this purpose, the nematode Caenorhabditis elegans served as a model animal. C. elegans fed a healthy food had an extended healthspan as compared to those fed a conventional diet. Then, utilizing this phenomenon, we clarified a mechanism of healthspan extension by measuring the single-worm ATP and estimating the ATP noise (or the variability of the ATP content) among individual worms and by quantitatively analyzing biodemographic data with the lifespan equation that was derived from a fluctuation theory

  2. Biophysical and biological meanings of healthspan from C. elegans cohort

    Energy Technology Data Exchange (ETDEWEB)

    Suda, Hitoshi, E-mail: suda@tsc.u-tokai.ac.jp

    2014-09-12

    Highlights: • We focus on a third factor, noise, as well as on genetic and environmental factors. • C. elegans fed a healthy food had an extended healthspan as compared to those fed a conventional diet. • An amplification of ATP noise was clearly evident from around the onset of biodemographic aging. • The extension of timing of noise amplification may contribute to effectively extending the healthspan. • The same mechanism of the mean lifespan extension in C. elegans may be realized in humans. - Abstract: Lifespan among individuals ranges widely in organisms from yeast to mammals, even in an isogenic cohort born in a nearly uniform environment. Needless to say, genetic and environmental factors are essential for aging and lifespan, but in addition, a third factor or the existence of a stochastic element must be reflected in aging and lifespan. An essential point is that lifespan or aging is an unpredictable phenomenon. The present study focuses on elucidating the biophysical and biological meanings of healthspan that latently indwells a stochastic nature. To perform this purpose, the nematode Caenorhabditis elegans served as a model animal. C. elegans fed a healthy food had an extended healthspan as compared to those fed a conventional diet. Then, utilizing this phenomenon, we clarified a mechanism of healthspan extension by measuring the single-worm ATP and estimating the ATP noise (or the variability of the ATP content) among individual worms and by quantitatively analyzing biodemographic data with the lifespan equation that was derived from a fluctuation theory.

  3. microRNA function in left-right neuronal asymmetry: perspectives from C. elegans.

    Science.gov (United States)

    Alqadah, Amel; Hsieh, Yi-Wen; Chuang, Chiou-Fen

    2013-09-23

    Left-right asymmetry in anatomical structures and functions of the nervous system is present throughout the animal kingdom. For example, language centers are localized in the left side of the human brain, while spatial recognition functions are found in the right hemisphere in the majority of the population. Disruption of asymmetry in the nervous system is correlated with neurological disorders. Although anatomical and functional asymmetries are observed in mammalian nervous systems, it has been a challenge to identify the molecular basis of these asymmetries. C. elegans has emerged as a prime model organism to investigate molecular asymmetries in the nervous system, as it has been shown to display functional asymmetries clearly correlated to asymmetric distribution and regulation of biologically relevant molecules. Small non-coding RNAs have been recently implicated in various aspects of neural development. Here, we review cases in which microRNAs are crucial for establishing left-right asymmetries in the C. elegans nervous system. These studies may provide insight into how molecular and functional asymmetries are established in the human brain.

  4. microRNA function in left-right neuronal asymmetry: perspectives from C. elegans

    Directory of Open Access Journals (Sweden)

    Amel eAlqadah

    2013-09-01

    Full Text Available Left-right asymmetry in anatomical structures and functions of the nervous system is present throughout the animal kingdom. For example, language centers are localized in the left side of the human brain, while spatial recognition functions are found in the right hemisphere in the majority of the population. Disruption of asymmetry in the nervous system is correlated with neurological disorders. Although anatomical and functional asymmetries are observed in mammalian nervous systems, it has been a challenge to identify the molecular basis of these asymmetries. C. elegans has emerged as a prime model organism to investigate molecular asymmetries in the nervous system, as it has been shown to display functional asymmetries clearly correlated to asymmetric distribution and regulation of biologically relevant molecules. Small non-coding RNAs have been recently implicated in various aspects of neural development. Here, we review cases in which microRNAs are crucial for establishing left-right asymmetries in the C. elegans nervous system. These studies may provide insight into how molecular and functional asymmetries are established in the human brain.

  5. Modeller af komplicerede systemer

    DEFF Research Database (Denmark)

    Mortensen, J.

    emphasizes their use in relation to technical systems. All the presented models, with the exception of the types presented in chapter 2, are non-theoretical non-formal conceptual network models. Two new model types are presented: 1) The System-Environment model, which describes the environments interaction...... with conceptual modeling in relation to process control. It´s purpose is to present classify and exemplify the use of a set of qualitative model types. Such model types are useful in the early phase of modeling, where no structured methods are at hand. Although the models are general in character, this thesis......This thesis, "Modeller af komplicerede systemer", represents part of the requirements for the Danish Ph.D.degree. Assisting professor John Nørgaard-Nielsen, M.Sc.E.E.Ph.D. has been principal supervisor and professor Morten Lind, M.Sc.E.E.Ph.D. has been assisting supervisor. The thesis is concerned...

  6. The systems integration modeling system

    International Nuclear Information System (INIS)

    Danker, W.J.; Williams, J.R.

    1990-01-01

    This paper discusses the systems integration modeling system (SIMS), an analysis tool for the detailed evaluation of the structure and related performance of the Federal Waste Management System (FWMS) and its interface with waste generators. It's use for evaluations in support of system-level decisions as to FWMS configurations, the allocation, sizing, balancing and integration of functions among elements, and the establishment of system-preferred waste selection and sequencing methods and other operating strategies is presented. SIMS includes major analysis submodels which quantify the detailed characteristics of individual waste items, loaded casks and waste packages, simulate the detailed logistics of handling and processing discrete waste items and packages, and perform detailed cost evaluations

  7. Shape memory alloy-based small crawling robots inspired by C. elegans

    Energy Technology Data Exchange (ETDEWEB)

    Yuk, Hyunwoo; Kim, Daeyeon; Shin, Jennifer H [Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Honggu; Jo, Sungho, E-mail: shjo@kaist.ac.kr, E-mail: j_shin@kaist.ac.kr [Department of Computer Science, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon (Korea, Republic of)

    2011-12-15

    Inspired by its simple musculature, actuation and motion mechanisms, we have developed a small crawling robot that closely mimics the model organism of our choice: Caenorhabditis elegans. A thermal shape memory alloy (SMA) was selected as an actuator due to the similarities of its properties to C. elegans muscles. Based on the anatomy of C. elegans, a 12-unit robot was designed to generate a sinusoidal undulating motion. Each body unit consisting of a pair of SMA actuators is serially connected by rigid links with an embedded motion control circuit. A simple binary operation-based motion control mechanism was implemented using a microcontroller. The assembled robot can execute C. elegans-like motion with a 0.17 Hz undulation frequency. Its motion is comparable to that of a real worm.

  8. Tracking and Quantifying Developmental Processes in C. elegans Using Open-source Tools.

    Science.gov (United States)

    Dutta, Priyanka; Lehmann, Christina; Odedra, Devang; Singh, Deepika; Pohl, Christian

    2015-12-16

    Quantitatively capturing developmental processes is crucial to derive mechanistic models and key to identify and describe mutant phenotypes. Here protocols are presented for preparing embryos and adult C. elegans animals for short- and long-term time-lapse microscopy and methods for tracking and quantification of developmental processes. The methods presented are all based on C. elegans strains available from the Caenorhabditis Genetics Center and on open-source software that can be easily implemented in any laboratory independently of the microscopy system used. A reconstruction of a 3D cell-shape model using the modelling software IMOD, manual tracking of fluorescently-labeled subcellular structures using the multi-purpose image analysis program Endrov, and an analysis of cortical contractile flow using PIVlab (Time-Resolved Digital Particle Image Velocimetry Tool for MATLAB) are shown. It is discussed how these methods can also be deployed to quantitatively capture other developmental processes in different models, e.g., cell tracking and lineage tracing, tracking of vesicle flow.

  9. Stereotypical Escape Behavior in Caenorhabditis elegans Allows Quantification of Effective Heat Stimulus Level.

    Directory of Open Access Journals (Sweden)

    Kawai Leung

    2016-12-01

    Full Text Available A goal of many sensorimotor studies is to quantify the stimulus-behavioral response relation for specific organisms and specific sensory stimuli. This is especially important to do in the context of painful stimuli since most animals in these studies cannot easily communicate to us their perceived levels of such noxious stimuli. Thus progress on studies of nociception and pain-like responses in animal models depends crucially on our ability to quantitatively and objectively infer the sensed levels of these stimuli from animal behaviors. Here we develop a quantitative model to infer the perceived level of heat stimulus from the stereotyped escape response of individual nematodes Caenorhabditis elegans stimulated by an IR laser. The model provides a method for quantification of analgesic-like effects of chemical stimuli or genetic mutations in C. elegans. We test ibuprofen-treated worms and a TRPV (transient receptor potential mutant, and we show that the perception of heat stimuli for the ibuprofen treated worms is lower than the wild-type. At the same time, our model shows that the mutant changes the worm's behavior beyond affecting the thermal sensory system. Finally, we determine the stimulus level that best distinguishes the analgesic-like effects and the minimum number of worms that allow for a statistically significant identification of these effects.

  10. Ultra-structural time-course study in the C. elegans model for Duchenne muscular dystrophy highlights a crucial role for sarcomere-anchoring structures and sarcolemma integrity in the earliest steps of the muscle degeneration process.

    Science.gov (United States)

    Brouilly, Nicolas; Lecroisey, Claire; Martin, Edwige; Pierson, Laura; Mariol, Marie-Christine; Qadota, Hiroshi; Labouesse, Michel; Streichenberger, Nathalie; Mounier, Nicole; Gieseler, Kathrin

    2015-11-15

    Duchenne muscular dystrophy (DMD) is a genetic disease characterized by progressive muscle degeneration due to mutations in the dystrophin gene. In spite of great advances in the design of curative treatments, most patients currently receive palliative therapies with steroid molecules such as prednisone or deflazacort thought to act through their immunosuppressive properties. These molecules only slightly slow down the progression of the disease and lead to severe side effects. Fundamental research is still needed to reveal the mechanisms involved in the disease that could be exploited as therapeutic targets. By studying a Caenorhabditis elegans model for DMD, we show here that dystrophin-dependent muscle degeneration is likely to be cell autonomous and affects the muscle cells the most involved in locomotion. We demonstrate that muscle degeneration is dependent on exercise and force production. Exhaustive studies by electron microscopy allowed establishing for the first time the chronology of subcellular events occurring during the entire process of muscle degeneration. This chronology highlighted the crucial role for dystrophin in stabilizing sarcomeric anchoring structures and the sarcolemma. Our results suggest that the disruption of sarcomeric anchoring structures and sarcolemma integrity, observed at the onset of the muscle degeneration process, triggers subcellular consequences that lead to muscle cell death. An ultra-structural analysis of muscle biopsies from DMD patients suggested that the chronology of subcellular events established in C. elegans models the pathogenesis in human. Finally, we found that the loss of sarcolemma integrity was greatly reduced after prednisone treatment suggesting a role for this molecule in plasma membrane stabilization. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. A fully automated microfluidic femtosecond laser axotomy platform for nerve regeneration studies in C. elegans.

    Science.gov (United States)

    Gokce, Sertan Kutal; Guo, Samuel X; Ghorashian, Navid; Everett, W Neil; Jarrell, Travis; Kottek, Aubri; Bovik, Alan C; Ben-Yakar, Adela

    2014-01-01

    Femtosecond laser nanosurgery has been widely accepted as an axonal injury model, enabling nerve regeneration studies in the small model organism, Caenorhabditis elegans. To overcome the time limitations of manual worm handling techniques, automation and new immobilization technologies must be adopted to improve throughput in these studies. While new microfluidic immobilization techniques have been developed that promise to reduce the time required for axotomies, there is a need for automated procedures to minimize the required amount of human intervention and accelerate the axotomy processes crucial for high-throughput. Here, we report a fully automated microfluidic platform for performing laser axotomies of fluorescently tagged neurons in living Caenorhabditis elegans. The presented automation process reduces the time required to perform axotomies within individual worms to ∼17 s/worm, at least one order of magnitude faster than manual approaches. The full automation is achieved with a unique chip design and an operation sequence that is fully computer controlled and synchronized with efficient and accurate image processing algorithms. The microfluidic device includes a T-shaped architecture and three-dimensional microfluidic interconnects to serially transport, position, and immobilize worms. The image processing algorithms can identify and precisely position axons targeted for ablation. There were no statistically significant differences observed in reconnection probabilities between axotomies carried out with the automated system and those performed manually with anesthetics. The overall success rate of automated axotomies was 67.4±3.2% of the cases (236/350) at an average processing rate of 17.0±2.4 s. This fully automated platform establishes a promising methodology for prospective genome-wide screening of nerve regeneration in C. elegans in a truly high-throughput manner.

  12. Lipid droplets as ubiquitous fat storage organelles in C. elegans

    Directory of Open Access Journals (Sweden)

    Guo Fengli

    2010-12-01

    Full Text Available Abstract Background Lipid droplets are a class of eukaryotic cell organelles for storage of neutral fat such as triacylglycerol (TAG and cholesterol ester (CE. We and others have recently reported that lysosome-related organelles (LROs are not fat storage structures in the nematode C. elegans. We also reported the formation of enlarged lipid droplets in a class of peroxisomal fatty acid β-oxidation mutants. In the present study, we seek to provide further evidence on the organelle nature and biophysical properties of fat storage structures in wild-type and mutant C. elegans. Results In this study, we provide biochemical, histological and ultrastructural evidence of lipid droplets in wild-type and mutant C. elegans that lack lysosome related organelles (LROs. The formation of lipid droplets and the targeting of BODIPY fatty acid analogs to lipid droplets in live animals are not dependent on lysosomal trafficking or peroxisome dysfunction. However, the targeting of Nile Red to lipid droplets in live animals occurs only in mutants with defective peroxisomes. Nile Red labelled-lipid droplets are characterized by a fluorescence emission spectrum distinct from that of Nile Red labelled-LROs. Moreover, we show that the recently developed post-fix Nile Red staining method labels lipid droplets exclusively. Conclusions Our results demonstrate lipid droplets as ubiquitous fat storage organelles and provide a unified explanation for previous studies on fat labelling methods in C. elegans. These results have important applications to the studies of fat storage and lipid droplet regulation in the powerful genetic system, C. elegans.

  13. Anti-inflammatory Lactobacillus rhamnosus CNCM I-3690 strain protects against oxidative stress and increases lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Gianfranco Grompone

    Full Text Available Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabditis elegans as host. C. elegans were fed on different LAB strains (78 in total and nematode viability was assessed after oxidative stress (3 mM and 5 mM H(2O(2. One strain, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and, also, increased average worm lifespan by 20%. Moreover, transcriptomic analysis of C. elegans fed with this strain showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans. This strain also had a clear anti-inflammatory profile when co-cultured with HT-29 cells, stimulated by pro-inflammatory cytokines, and co-culture systems with HT-29 cells and DC in the presence of LPS. Finally, this Lactobacillus strain reduced inflammation in a murine model of colitis. This work suggests that C. elegans is a fast, predictive and convenient screening tool to identify new potential antioxidant probiotic strains for subsequent use in humans.

  14. Anti-Inflammatory Lactobacillus rhamnosus CNCM I-3690 Strain Protects against Oxidative Stress and Increases Lifespan in Caenorhabditis elegans

    Science.gov (United States)

    Grompone, Gianfranco; Martorell, Patricia; Llopis, Silvia; González, Núria; Genovés, Salvador; Mulet, Ana Paula; Fernández-Calero, Tamara; Tiscornia, Inés; Bollati-Fogolín, Mariela; Chambaud, Isabelle; Foligné, Benoit; Montserrat, Agustín; Ramón, Daniel

    2012-01-01

    Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB) administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabditis elegans as host. C. elegans were fed on different LAB strains (78 in total) and nematode viability was assessed after oxidative stress (3 mM and 5 mM H2O2). One strain, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and, also, increased average worm lifespan by 20%. Moreover, transcriptomic analysis of C. elegans fed with this strain showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans. This strain also had a clear anti-inflammatory profile when co-cultured with HT-29 cells, stimulated by pro-inflammatory cytokines, and co-culture systems with HT-29 cells and DC in the presence of LPS. Finally, this Lactobacillus strain reduced inflammation in a murine model of colitis. This work suggests that C. elegans is a fast, predictive and convenient screening tool to identify new potential antioxidant probiotic strains for subsequent use in humans. PMID:23300685

  15. A DOG’s View of Fanconi Anemia: Insights from C. elegans

    Directory of Open Access Journals (Sweden)

    Martin Jones

    2012-01-01

    Full Text Available C. elegans provides an excellent model system for the study of the Fanconi Anemia (FA, one of the hallmarks of which is sensitivity to interstrand crosslinking agents. Central to our understanding of FA has been the investigation of DOG-1, the functional ortholog of the deadbox helicase FANCJ. Here we review the current understanding of the unique role of DOG-1 in maintaining stability of G-rich DNA in C. elegans and explore the question of why DOG-1 animals are crosslink sensitive. We propose a dynamic model in which noncovalently linked G-rich structures form and un-form in the presence of DOG-1. When DOG-1 is absent but crosslinking agents are present the G-rich structures are readily covalently crosslinked, resulting in increased crosslinks formation and thus giving increased crosslink sensitivity. In this interpretation DOG-1 is neither upstream nor downstream in the FA pathway, but works alongside it to limit the availability of crosslink substrates. This model reconciles the crosslink sensitivity observed in the absence of DOG-1 function with its unique role in maintaining G-Rich DNA and will help to formulate experiments to test this hypothesis.

  16. Biological responsiveness to the phorbol esters and specific binding of [3H]phorbol 12,13-dibutyrate in the nematode Caenorhabditis elegans, a manipulable genetic system

    International Nuclear Information System (INIS)

    Lew, K.K.; Chritton, S.; Blumberg, P.M.

    1982-01-01

    Because of its suitability for genetic studies, the nematode Caenorhabditis elegans was examined for its responsiveness to the phorbol esters. Phorbol 12-myristate 13-acetate had three effects. It inhibited the increase in animal size during growth; it decreased the yield of progeny; and it caused uncoordinated movement of the adult. The effects on nematode size, progeny yield, and movement were quantitated. Concentrations of phorbol 12-myristate 13-acetate yielding half-maximal responses were 440, 460, and 170 nM, respectively. As was expected from the biological responsiveness of the nematodes, specific, saturable binding of phorbol ester to nematode extracts was found. [ 3 H]phorbol 12,13-dibutyrate bound with a dissociation constant of 26.8 +/- 3.9 nM. At saturation, 5.7 +/- 1.4 pmole/mg protein was bound

  17. The Earth System Model

    Science.gov (United States)

    Schoeberl, Mark; Rood, Richard B.; Hildebrand, Peter; Raymond, Carol

    2003-01-01

    The Earth System Model is the natural evolution of current climate models and will be the ultimate embodiment of our geophysical understanding of the planet. These models are constructed from components - atmosphere, ocean, ice, land, chemistry, solid earth, etc. models and merged together through a coupling program which is responsible for the exchange of data from the components. Climate models and future earth system models will have standardized modules, and these standards are now being developed by the ESMF project funded by NASA. The Earth System Model will have a variety of uses beyond climate prediction. The model can be used to build climate data records making it the core of an assimilation system, and it can be used in OSSE experiments to evaluate. The computing and storage requirements for the ESM appear to be daunting. However, the Japanese ES theoretical computing capability is already within 20% of the minimum requirements needed for some 2010 climate model applications. Thus it seems very possible that a focused effort to build an Earth System Model will achieve succcss.

  18. Distinct pathogenesis and host responses during infection of C. elegans by P. aeruginosa and S. aureus.

    Science.gov (United States)

    Irazoqui, Javier E; Troemel, Emily R; Feinbaum, Rhonda L; Luhachack, Lyly G; Cezairliyan, Brent O; Ausubel, Frederick M

    2010-07-01

    The genetically tractable model host Caenorhabditis elegans provides a valuable tool to dissect host-microbe interactions in vivo. Pseudomonas aeruginosa and Staphylococcus aureus utilize virulence factors involved in human disease to infect and kill C. elegans. Despite much progress, virtually nothing is known regarding the cytopathology of infection and the proximate causes of nematode death. Using light and electron microscopy, we found that P. aeruginosa infection entails intestinal distention, accumulation of an unidentified extracellular matrix and P. aeruginosa-synthesized outer membrane vesicles in the gut lumen and on the apical surface of intestinal cells, the appearance of abnormal autophagosomes inside intestinal cells, and P. aeruginosa intracellular invasion of C. elegans. Importantly, heat-killed P. aeruginosa fails to elicit a significant host response, suggesting that the C. elegans response to P. aeruginosa is activated either by heat-labile signals or pathogen-induced damage. In contrast, S. aureus infection causes enterocyte effacement, intestinal epithelium destruction, and complete degradation of internal organs. S. aureus activates a strong transcriptional response in C. elegans intestinal epithelial cells, which aids host survival during infection and shares elements with human innate responses. The C. elegans genes induced in response to S. aureus are mostly distinct from those induced by P. aeruginosa. In contrast to P. aeruginosa, heat-killed S. aureus activates a similar response as live S. aureus, which appears to be independent of the single C. elegans Toll-Like Receptor (TLR) protein. These data suggest that the host response to S. aureus is possibly mediated by pathogen-associated molecular patterns (PAMPs). Because our data suggest that neither the P. aeruginosa nor the S. aureus-triggered response requires canonical TLR signaling, they imply the existence of unidentified mechanisms for pathogen detection in C. elegans, with

  19. Distinct pathogenesis and host responses during infection of C. elegans by P. aeruginosa and S. aureus.

    Directory of Open Access Journals (Sweden)

    Javier E Irazoqui

    2010-07-01

    Full Text Available The genetically tractable model host Caenorhabditis elegans provides a valuable tool to dissect host-microbe interactions in vivo. Pseudomonas aeruginosa and Staphylococcus aureus utilize virulence factors involved in human disease to infect and kill C. elegans. Despite much progress, virtually nothing is known regarding the cytopathology of infection and the proximate causes of nematode death. Using light and electron microscopy, we found that P. aeruginosa infection entails intestinal distention, accumulation of an unidentified extracellular matrix and P. aeruginosa-synthesized outer membrane vesicles in the gut lumen and on the apical surface of intestinal cells, the appearance of abnormal autophagosomes inside intestinal cells, and P. aeruginosa intracellular invasion of C. elegans. Importantly, heat-killed P. aeruginosa fails to elicit a significant host response, suggesting that the C. elegans response to P. aeruginosa is activated either by heat-labile signals or pathogen-induced damage. In contrast, S. aureus infection causes enterocyte effacement, intestinal epithelium destruction, and complete degradation of internal organs. S. aureus activates a strong transcriptional response in C. elegans intestinal epithelial cells, which aids host survival during infection and shares elements with human innate responses. The C. elegans genes induced in response to S. aureus are mostly distinct from those induced by P. aeruginosa. In contrast to P. aeruginosa, heat-killed S. aureus activates a similar response as live S. aureus, which appears to be independent of the single C. elegans Toll-Like Receptor (TLR protein. These data suggest that the host response to S. aureus is possibly mediated by pathogen-associated molecular patterns (PAMPs. Because our data suggest that neither the P. aeruginosa nor the S. aureus-triggered response requires canonical TLR signaling, they imply the existence of unidentified mechanisms for pathogen detection in C

  20. RSMASS system model development

    International Nuclear Information System (INIS)

    Marshall, A.C.; Gallup, D.R.

    1998-01-01

    RSMASS system mass models have been used for more than a decade to make rapid estimates of space reactor power system masses. This paper reviews the evolution of the RSMASS models and summarizes present capabilities. RSMASS has evolved from a simple model used to make rough estimates of space reactor and shield masses to a versatile space reactor power system model. RSMASS uses unique reactor and shield models that permit rapid mass optimization calculations for a variety of space reactor power and propulsion systems. The RSMASS-D upgrade of the original model includes algorithms for the balance of the power system, a number of reactor and shield modeling improvements, and an automatic mass optimization scheme. The RSMASS-D suite of codes cover a very broad range of reactor and power conversion system options as well as propulsion and bimodal reactor systems. Reactor choices include in-core and ex-core thermionic reactors, liquid metal cooled reactors, particle bed reactors, and prismatic configuration reactors. Power conversion options include thermoelectric, thermionic, Stirling, Brayton, and Rankine approaches. Program output includes all major component masses and dimensions, efficiencies, and a description of the design parameters for a mass optimized system. In the past, RSMASS has been used as an aid to identify and select promising concepts for space power applications. The RSMASS modeling approach has been demonstrated to be a valuable tool for guiding optimization of the power system design; consequently, the model is useful during system design and development as well as during the selection process. An improved in-core thermionic reactor system model RSMASS-T is now under development. The current development of the RSMASS-T code represents the next evolutionary stage of the RSMASS models. RSMASS-T includes many modeling improvements and is planned to be more user-friendly. RSMASS-T will be released as a fully documented, certified code at the end of

  1. Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways.

    Science.gov (United States)

    Yuen, Grace J; Ausubel, Frederick M

    2018-12-31

    The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection.

  2. Pheromone modulates two phenotypically plastic traits - adult reproduction and larval diapause - in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Wharam, Barney; Weldon, Laura; Viney, Mark

    2017-08-22

    Animals use information from their environment to make decisions, ultimately to maximize their fitness. The nematode C. elegans has a pheromone signalling system, which hitherto has principally been thought to be used by worms in deciding whether or not to arrest their development as larvae. Recent studies have suggested that this pheromone can have other roles in the C. elegans life cycle. Here we demonstrate a new role for the C. elegans pheromone, showing that it accelerates hermaphrodites' reproductive rate, a phenomenon which we call pheromone-dependent reproductive plasticity (PDRP). We also find that pheromone accelerates larval growth rates, but this depends on a live bacterial food source, while PDRP does not. Different C. elegans strains all show PDRP, though the magnitude of these effects differ among the strains, which is analogous to the diversity of arrested larval phenotypes that this pheromone also induces. Using a selection experiment we also show that selection for PDRP or for larval arrest affects both the target and the non-target trait, suggesting that there is cross-talk between these two pheromone-dependent traits. Together, these results show that C. elegans' pheromone is a signal that acts at two key life cycle points, controlling alternative larval fates and affecting adult hermaphrodites' reproduction. More broadly, these results suggest that to properly understand and interpret the biology of pheromone signalling in C. elegans and other nematodes, the life-history biology of these organisms in their natural environment needs to be considered.

  3. Systemic resilience model

    International Nuclear Information System (INIS)

    Lundberg, Jonas; Johansson, Björn JE

    2015-01-01

    It has been realized that resilience as a concept involves several contradictory definitions, both for instance resilience as agile adjustment and as robust resistance to situations. Our analysis of resilience concepts and models suggest that beyond simplistic definitions, it is possible to draw up a systemic resilience model (SyRes) that maintains these opposing characteristics without contradiction. We outline six functions in a systemic model, drawing primarily on resilience engineering, and disaster response: anticipation, monitoring, response, recovery, learning, and self-monitoring. The model consists of four areas: Event-based constraints, Functional Dependencies, Adaptive Capacity and Strategy. The paper describes dependencies between constraints, functions and strategies. We argue that models such as SyRes should be useful both for envisioning new resilience methods and metrics, as well as for engineering and evaluating resilient systems. - Highlights: • The SyRes model resolves contradictions between previous resilience definitions. • SyRes is a core model for envisioning and evaluating resilience metrics and models. • SyRes describes six functions in a systemic model. • They are anticipation, monitoring, response, recovery, learning, self-monitoring. • The model describes dependencies between constraints, functions and strategies

  4. [Specification of cell destiny in early Caenorhabditis elegans embryo].

    Science.gov (United States)

    Schierenberg, E

    1997-02-01

    Embryogenesis of the nematode Caenorhabditis elegans has been described completely on a cell-by-cell basis and found to be essentially invariant. With this knowledge in hands, micromanipulated embryos and mutants have been analyzed for cell lineage defects and the distribution of specific gene products. The results challenge the classical view of cell-autonomous development in nematodes and indicate that the early embryo of C. elegans is a highly dynamic system. A network of inductive events between neighboring cells is being revealed, which is necessary to assign different developmental programs to blastomeres. In those cases where molecules involved in these cell-cell interactions have been identified, homologies to cell surface receptors, ligands and transcription factors found in other systems have become obvious.

  5. Selected System Models

    Science.gov (United States)

    Schmidt-Eisenlohr, F.; Puñal, O.; Klagges, K.; Kirsche, M.

    Apart from the general issue of modeling the channel, the PHY and the MAC of wireless networks, there are specific modeling assumptions that are considered for different systems. In this chapter we consider three specific wireless standards and highlight modeling options for them. These are IEEE 802.11 (as example for wireless local area networks), IEEE 802.16 (as example for wireless metropolitan networks) and IEEE 802.15 (as example for body area networks). Each section on these three systems discusses also at the end a set of model implementations that are available today.

  6. Spreading of a prion domain from cell-to-cell by vesicular transport in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Carmen I Nussbaum-Krammer

    2013-03-01

    Full Text Available Prion proteins can adopt self-propagating alternative conformations that account for the infectious nature of transmissible spongiform encephalopathies (TSEs and the epigenetic inheritance of certain traits in yeast. Recent evidence suggests a similar propagation of misfolded proteins in the spreading of pathology of neurodegenerative diseases including Alzheimer's or Parkinson's disease. Currently there is only a limited number of animal model systems available to study the mechanisms that underlie the cell-to-cell transmission of aggregation-prone proteins. Here, we have established a new metazoan model in Caenorhabditis elegans expressing the prion domain NM of the cytosolic yeast prion protein Sup35, in which aggregation and toxicity are dependent upon the length of oligopeptide repeats in the glutamine/asparagine (Q/N-rich N-terminus. NM forms multiple classes of highly toxic aggregate species and co-localizes to autophagy-related vesicles that transport the prion domain from the site of expression to adjacent tissues. This is associated with a profound cell autonomous and cell non-autonomous disruption of mitochondrial integrity, embryonic and larval arrest, developmental delay, widespread tissue defects, and loss of organismal proteostasis. Our results reveal that the Sup35 prion domain exhibits prion-like properties when expressed in the multicellular organism C. elegans and adapts to different requirements for propagation that involve the autophagy-lysosome pathway to transmit cytosolic aggregation-prone proteins between tissues.

  7. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  8. Ascaroside expression in Caenorhabditis elegans is strongly dependent on diet and developmental stage.

    Directory of Open Access Journals (Sweden)

    Fatma Kaplan

    2011-03-01

    from previous studies, our results show that the pheromone system of C. elegans mimics that of insects in many ways, suggesting that pheromone signaling in C. elegans may exhibit functional homology also at the sensory level. In addition, our results provide a strong foundation for future behavioral modeling studies.

  9. Big Data in Caenorhabditis elegans: quo vadis?

    Science.gov (United States)

    Hutter, Harald; Moerman, Donald

    2015-11-05

    A clear definition of what constitutes "Big Data" is difficult to identify, but we find it most useful to define Big Data as a data collection that is complete. By this criterion, researchers on Caenorhabditis elegans have a long history of collecting Big Data, since the organism was selected with the idea of obtaining a complete biological description and understanding of development. The complete wiring diagram of the nervous system, the complete cell lineage, and the complete genome sequence provide a framework to phrase and test hypotheses. Given this history, it might be surprising that the number of "complete" data sets for this organism is actually rather small--not because of lack of effort, but because most types of biological experiments are not currently amenable to complete large-scale data collection. Many are also not inherently limited, so that it becomes difficult to even define completeness. At present, we only have partial data on mutated genes and their phenotypes, gene expression, and protein-protein interaction--important data for many biological questions. Big Data can point toward unexpected correlations, and these unexpected correlations can lead to novel investigations; however, Big Data cannot establish causation. As a result, there is much excitement about Big Data, but there is also a discussion on just what Big Data contributes to solving a biological problem. Because of its relative simplicity, C. elegans is an ideal test bed to explore this issue and at the same time determine what is necessary to build a multicellular organism from a single cell. © 2015 Hutter and Moerman. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  10. Chemical constituents and biological activities of Dianthus elegans var. elegans.

    Science.gov (United States)

    Mutlu, Kiymet; Sarikahya, Nazli Boke; Nalbantsoy, Ayse; Kirmizigul, Suheyla

    2018-06-01

    Chemical investigation of the aerial parts of Dianthus elegans var. elegans afforded two previously undescribed saponins, named dianosides M-N (1-2), together with four oleanane-type triterpenoid glycosides (3-6). Their structures were elucidated as 3-O-α-L-arabinofuranosyl-16α-hydroxyolean-12-ene-23α, 28β-dioic acid (1) and 3-O-α-L-arabinofuranosyl-(1 → 3)-β-D-glucopyranosyl 16α-hydroxyolean-12-ene-23α-oic acid, 28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glycosyl ester (2) by chemical and extensive spectroscopic methods including IR, 1D, 2D NMR and HRESIMS. Both of the saponins were evaluated for their cytotoxicities against HEK-293, A-549 and HeLa human cancer cells using the MTT method. All compounds showed no substantial cytotoxic activity against tested cell lines. However, dianosides M-N and the n-butanol fraction exhibited considerable haemolysis in human erythrocyte cells. The immunomodulatory properties of dianosides M-N were also evaluated in activated whole blood cells by PMA plus ionomycin. Dianosides M-N increased IL-1β concentration significantly whereas the n-butanol fraction slightly augmented IL-1β secretion. All compounds did not change IL-2 and IFN-γ levels considerably.

  11. Cell cycle accumulation of the proliferating cell nuclear antigen PCN-1 transitions from continuous in the adult germline to intermittent in the early embryo of C. elegans.

    Science.gov (United States)

    Kocsisova, Zuzana; Kornfeld, Kerry; Schedl, Tim

    2018-05-30

    The proliferating cell nuclear antigen (PCNA or PCN-1 in C. elegans), an essential processivity factor for DNA polymerase δ, has been widely used as a marker of S-phase. In C. elegans early embryos, PCN-1 accumulation is cyclic, localizing to the nucleus during S-phase and the cytoplasm during the rest of the cell cycle. The C. elegans larval and adult germline is an important model systems for studying cell cycle regulation, and it was observed that the cell cycle regulator cyclin E (CYE-1 in C. elegans) displays a non-cyclic, continuous accumulation pattern in this tissue. The accumulation pattern of PCN-1 has not been well defined in the larval and adult germline, and the objective of this study was to determine if the accumulation pattern is cyclic, as in other cells and organisms, or continuous, similar to cyclin E. To study the larval and adult germline accumulation of PCN-1 expressed from its native locus, we used CRISPR/Cas9 technology to engineer a novel allele of pcn-1 that encodes an epitope-tagged protein. S-phase nuclei were labeled using EdU nucleotide incorporation, and FLAG::PCN-1 was detected by antibody staining. All progenitor zone nuclei, including those that were not in S-phase (as they were negative for EdU staining) showed PCN-1 accumulation, indicating that PCN-1 accumulated during all cell cycle phases in the germline progenitor zone. The same result was observed with a GFP::PCN-1 fusion protein expressed from a transgene. pcn-1 loss-of-function mutations were analyzed, and pcn-1 was necessary for robust fertility and embryonic development. In the C. elegans early embryo as well as other organisms, PCN-1 accumulates in nuclei only during S-phase. By contrast, in the progenitor zone of the germline of C. elegans, PCN-1 accumulated in nuclei during all cell cycle stages. This pattern is similar to accumulation pattern of cyclin E. These observations support the model that mitotic cell cycle regulation in the germline stem and progenitor

  12. A semi-automated motion-tracking analysis of locomotion speed in the C. elegans transgenics overexpressing beta-amyloid in neurons

    Directory of Open Access Journals (Sweden)

    Kevin eMachino

    2014-07-01

    Full Text Available Multi-Worm Tracker (MWT is a real-time computer vision system that can simultaneously quantify motional patterns of multiple worms. MWT provides several behavioral parameters, including analysis of accurate real-time locomotion speed in the nematode, Caenorhabditis elegans. Here, we determined locomotion speed of the Alzheimer’s disease (AD transgenic strain that over-expresses human beta-amyloid1-42 (Aβ in the neurons. The MWT analysis showed that the AD strain logged a slower average speed than the wild type worms. The results may be consistent with the observation that the AD patients with dementia tend to show deficits in physical activities, including frequent falls. The AD strain showed reduced ability of the eggs to hatch and slowed hatching of the eggs. Thus, over-expression of Aβ in neurons causes negative effects on locomotion and hatchability. This study sheds light on new examples of detrimental effects that Aβ deposits can exhibit using C. elegans as a model system. The information gathered from this study indicates that the motion tracking analysis is a cost-effective, efficient way to assess the deficits of Aβ over-expression in the C. elegans system.

  13. Expression of mammalian GPCRs in C. elegans generates novel behavioural responses to human ligands

    Directory of Open Access Journals (Sweden)

    Jansen Gert

    2006-07-01

    Full Text Available Abstract Background G-protein-coupled receptors (GPCRs play a crucial role in many biological processes and represent a major class of drug targets. However, purification of GPCRs for biochemical study is difficult and current methods of studying receptor-ligand interactions involve in vitro systems. Caenorhabditis elegans is a soil-dwelling, bacteria-feeding nematode that uses GPCRs expressed in chemosensory neurons to detect bacteria and environmental compounds, making this an ideal system for studying in vivo GPCR-ligand interactions. We sought to test this by functionally expressing two medically important mammalian GPCRs, somatostatin receptor 2 (Sstr2 and chemokine receptor 5 (CCR5 in the gustatory neurons of C. elegans. Results Expression of Sstr2 and CCR5 in gustatory neurons allow C. elegans to specifically detect and respond to somatostatin and MIP-1α respectively in a robust avoidance assay. We demonstrate that mammalian heterologous GPCRs can signal via different endogenous Gα subunits in C. elegans, depending on which cells it is expressed in. Furthermore, pre-exposure of GPCR transgenic animals to its ligand leads to receptor desensitisation and behavioural adaptation to subsequent ligand exposure, providing further evidence of integration of the mammalian GPCRs into the C. elegans sensory signalling machinery. In structure-function studies using a panel of somatostatin-14 analogues, we identified key residues involved in the interaction of somatostatin-14 with Sstr2. Conclusion Our results illustrate a remarkable evolutionary plasticity in interactions between mammalian GPCRs and C. elegans signalling machinery, spanning 800 million years of evolution. This in vivo system, which imparts novel avoidance behaviour on C. elegans, thus provides a simple means of studying and screening interaction of GPCRs with extracellular agonists, antagonists and intracellular binding partners.

  14. Analysis of C. elegans NR2E nuclear receptors defines three conserved clades and ligand-independent functions

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    Weber Katherine P

    2012-06-01

    Full Text Available Abstract Background The nuclear receptors (NRs are an important class of transcription factors that are conserved across animal phyla. Canonical NRs consist of a DNA-binding domain (DBD and ligand-binding domain (LBD. While most animals have 20–40 NRs, nematodes of the genus Caenorhabditis have experienced a spectacular proliferation and divergence of NR genes. The LBDs of evolutionarily-conserved Caenorhabditis NRs have diverged sharply from their Drosophila and vertebrate orthologs, while the DBDs have been strongly conserved. The NR2E family of NRs play critical roles in development, especially in the nervous system. In this study, we explore the phylogenetics and function of the NR2E family of Caenorhabditis elegans, using an in vivo assay to test LBD function. Results Phylogenetic analysis reveals that the NR2E family of NRs consists of three broadly-conserved clades of orthologous NRs. In C. elegans, these clades are defined by nhr-67, fax-1 and nhr-239. The vertebrate orthologs of nhr-67 and fax-1 are Tlx and PNR, respectively. While the nhr-239 clade includes orthologs in insects (Hr83, an echinoderm, and a hemichordate, the gene appears to have been lost from vertebrate lineages. The C. elegans and C. briggsae nhr-239 genes have an apparently-truncated and highly-diverged LBD region. An additional C. elegans NR2E gene, nhr-111, appears to be a recently-evolved paralog of fax-1; it is present in C. elegans, but not C. briggsae or other animals with completely-sequenced genomes. Analysis of the relatively unstudied nhr-111 and nhr-239 genes demonstrates that they are both expressed—nhr-111 very broadly and nhr-239 in a small subset of neurons. Analysis of the FAX-1 LBD in an in vivo assay revealed that it is not required for at least some developmental functions. Conclusions Our analysis supports three conserved clades of NR2E receptors, only two of which are represented in vertebrates, indicating three ancestral NR2E genes in the

  15. Function and regulation of lipid biology in Caenorhabditis elegans aging

    Directory of Open Access Journals (Sweden)

    Nicole Shangming Hou

    2012-05-01

    Full Text Available Rapidly expanding aging populations and a concomitant increase in the prevalence of age-related diseases are global health problems today. Over the past three decades, a large body of work has led to the identification of genes and regulatory networks that affect longevity and health span, often benefitting from the tremendous power of genetics in vertebrate and invertebrate model organisms. Interestingly, many of these factors appear linked to lipids, important molecules that participate in cellular signaling, energy metabolism, and structural compartmentalization. Despite the putative link between lipids and longevity, the role of lipids in aging remains poorly understood. Emerging data from the model organism Caenorhabditis elegans suggest that lipid composition may change during aging, as several pathways that influence aging also regulate lipid metabolism enzymes; moreover, some of these enzymes apparently play key roles in the pathways that affect the rate of aging. By understanding how lipid biology is regulated during C. elegans aging, and how it impacts molecular, cellular and organismal function, we may gain insight into novel ways to delay aging using genetic or pharmacological interventions. In the present review we discuss recent insights into the roles of lipids in C. elegans aging, including regulatory roles played by lipids themselves, the regulation of lipid metabolic enzymes, and the roles of lipid metabolism genes in the pathways that affect aging.

  16. Antifungal chemical compounds identified using a C. elegans pathogenicity assay.

    Directory of Open Access Journals (Sweden)

    Julia Breger

    2007-02-01

    Full Text Available There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2% that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi.

  17. Nanoscale Mechanical Stimulation Method for Quantifying C. elegans Mechanosensory Behavior and Memory.

    Science.gov (United States)

    Sugi, Takuma; Okumura, Etsuko; Kiso, Kaori; Igarashi, Ryuji

    2016-01-01

    Withdrawal escape response of C. elegans to nonlocalized vibration is a useful behavioral paradigm to examine mechanisms underlying mechanosensory behavior and its memory-dependent change. However, there are very few methods for investigating the degree of vibration frequency, amplitude and duration needed to induce behavior and memory. Here, we establish a new system to quantify C. elegans mechanosensory behavior and memory using a piezoelectric sheet speaker. In the system, we can flexibly change the vibration properties at a nanoscale displacement level and quantify behavioral responses under each vibration property. This system is an economic setup and easily replicated in other laboratories. By using the system, we clearly detected withdrawal escape responses and confirmed habituation memory. This system will facilitate the understanding of physiological aspects of C. elegans mechanosensory behavior in the future.

  18. Modeling Sustainable Food Systems.

    Science.gov (United States)

    Allen, Thomas; Prosperi, Paolo

    2016-05-01

    The processes underlying environmental, economic, and social unsustainability derive in part from the food system. Building sustainable food systems has become a predominating endeavor aiming to redirect our food systems and policies towards better-adjusted goals and improved societal welfare. Food systems are complex social-ecological systems involving multiple interactions between human and natural components. Policy needs to encourage public perception of humanity and nature as interdependent and interacting. The systemic nature of these interdependencies and interactions calls for systems approaches and integrated assessment tools. Identifying and modeling the intrinsic properties of the food system that will ensure its essential outcomes are maintained or enhanced over time and across generations, will help organizations and governmental institutions to track progress towards sustainability, and set policies that encourage positive transformations. This paper proposes a conceptual model that articulates crucial vulnerability and resilience factors to global environmental and socio-economic changes, postulating specific food and nutrition security issues as priority outcomes of food systems. By acknowledging the systemic nature of sustainability, this approach allows consideration of causal factor dynamics. In a stepwise approach, a logical application is schematized for three Mediterranean countries, namely Spain, France, and Italy.

  19. Research progress in neuro-immune interactions in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Jin-ling CAI

    2012-09-01

    Full Text Available The innate immune response may be activated quickly once the organism is invaded by exotic pathogens. An excessive immune response may result in inflammation and tissue damage, whereas an insufficient immune response may result in infection. Nervous system may regulate the intensity of innate immune responses by releasing neurotransmitters, neuropeptides and hormones. Compared with the complicated neuro-immune system in mammals, it is much simpler in Caenorhabditis elegans. Besides, C. elegans is accessible to genetic, molecular biology and behavioral analyses, so it has been used in studies on neuro-immune interactions. It has been revealed recently in the studies with C. elegans that the neuronal pathways regulating innate immune responses primarily include a transforming growth factor-β (TGF-β pathway, an insulin/insulin-like growth factor receptor (IGF pathway and dopaminergic neurotransmission. Since these pathways are evolutionally conservative, so it might be able to provide some new ideas for the research on neuro-immune interactions at molecular levels. The recent progress in this field has been reviewed in present paper.

  20. A high-throughput method for assessing chemical toxicity using a Caenorhabditis elegans reproduction assay

    International Nuclear Information System (INIS)

    Boyd, Windy A.; McBride, Sandra J.; Rice, Julie R.; Snyder, Daniel W.; Freedman, Jonathan H.

    2010-01-01

    The National Research Council has outlined the need for non-mammalian toxicological models to test the potential health effects of a large number of chemicals while also reducing the use of traditional animal models. The nematode Caenorhabditis elegans is an attractive alternative model because of its well-characterized and evolutionarily conserved biology, low cost, and ability to be used in high-throughput screening. A high-throughput method is described for quantifying the reproductive capacity of C. elegans exposed to chemicals for 48 h from the last larval stage (L4) to adulthood using a COPAS Biosort. Initially, the effects of exposure conditions that could influence reproduction were defined. Concentrations of DMSO vehicle ≤ 1% did not affect reproduction. Previous studies indicated that C. elegans may be influenced by exposure to low pH conditions. At pHs greater than 4.5, C. elegans reproduction was not affected; however below this pH there was a significant decrease in the number of offspring. Cadmium chloride was chosen as a model toxicant to verify that automated measurements were comparable to those of traditional observational studies. EC 50 values for cadmium for automated measurements (176-192 μM) were comparable to those previously reported for a 72-h exposure using manual counting (151 μM). The toxicity of seven test toxicants on C. elegans reproduction was highly correlative with rodent lethality suggesting that this assay may be useful in predicting the potential toxicity of chemicals in other organisms.

  1. Selenocysteine modulates resistance to environmental stress and confers anti-aging effects in C. elegans.

    Science.gov (United States)

    Kim, Jun-Sung; Kim, So-Hyeon; Park, Sang-Kyu

    2017-08-01

    The free radical theory of aging suggests that cellular oxidative damage caused by free radicals is a leading cause of aging. In the present study, we examined the effects of a well-known anti-oxidant amino acid derivative, selenocysteine, in response to environmental stress and aging using Caenorhabditis elegans as a model system. The response to oxidative stress induced by H2O2 or ultraviolet irradiation was compared between the untreated control and selenocysteine-treated groups. The effect of selenocysteine on lifespan and fertility was then determined. To examine the effect of selenocysteine on muscle aging, we monitored the change in motility with aging in both the untreated control and selenocysteine-treated groups. Dietary supplementation with selenocysteine significantly increased resistance to oxidative stress. Survival after ultraviolet irradiation was also increased by supplementation with selenocysteine. Treatment with selenocysteine confers a longevity phenotype without an accompanying reduction in fertility, which is frequently observed in lifespan-extending interventions as a trade-off in C. elegans. In addition, the age-related decline in motility was significantly delayed by supplementation of selenocysteine. These findings suggest that dietary supplementation of selenocysteine can modulate response to stressors and lead to lifespan extension, thus supporting the free radical theory of aging.

  2. Bioactive Peptides from Angelica sinensis Protein Hydrolyzate Delay Senescence in Caenorhabditis elegans through Antioxidant Activities

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    Qiangqiang Wang

    2016-01-01

    Full Text Available Since excessive reactive oxygen species (ROS is known to be associated with aging and age-related diseases, strategies modulating ROS level and antioxidant defense systems may contribute to the delay of senescence. Here we show that the protein hydrolyzate from Angelica sinensis was capable of increasing oxidative survival of the model animal Caenorhabditis elegans intoxicated by paraquat. The hydrolyzate was then fractionated by ultrafiltration, and the antioxidant fraction (<3 kDa was purified by gel filtration to obtain the antioxidant A. sinensis peptides (AsiPeps, which were mostly composed of peptides with <20 amino acid residues. Further studies demonstrate that AsiPeps were able to reduce the endogenous ROS level, increase the activities of the antioxidant enzymes superoxide dismutase and catalase, and decrease the content of the lipid peroxidation product malondialdehyde in nematodes treated with paraquat or undergoing senescence. AsiPeps were also shown to reduce age pigments accumulation and extend lifespan but did not affect the food-intake behavior of the nematodes. Taken together, our results demonstrate that A. sinensis peptides (AsiPeps are able to delay aging process in C. elegans through antioxidant activities independent of dietary restriction.

  3. Astragalus Polysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity in Caenorhabditis elegans

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    Haifeng Li

    2016-01-01

    Full Text Available Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson’s disease (PD. However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA, a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic gene egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential of Astragalus polysaccharide in neurodegeneration.

  4. Catalpol Modulates Lifespan via DAF-16/FOXO and SKN-1/Nrf2 Activation in Caenorhabditis elegans

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    Hyun Won Seo

    2015-01-01

    Full Text Available Catalpol is an effective component of rehmannia root and known to possess various pharmacological properties. The present study was aimed at investigating the potential effects of catalpol on the lifespan and stress tolerance using C. elegans model system. Herein, catalpol showed potent lifespan extension of wild-type nematode under normal culture condition. In addition, survival rate of catalpol-fed nematodes was significantly elevated compared to untreated control under heat and oxidative stress but not under hyperosmolality conditions. We also found that elevated antioxidant enzyme activities and expressions of stress resistance proteins were attributed to catalpol-mediated increased stress tolerance of nematode. We further investigated whether catalpol’s longevity effect is related to aging-related factors including reproduction, food intake, and growth. Interestingly, catalpol exposure could attenuate pharyngeal pumping rate, indicating that catalpol may induce dietary restriction of nematode. Moreover, locomotory ability of aged nematode was significantly improved by catalpol treatment, while lipofuscin levels were attenuated, suggesting that catalpol may affect age-associated changes of nematode. Our mechanistic studies revealed that mek-1, daf-2, age-1, daf-16, and skn-1 are involved in catalpol-mediated longevity. These results indicate that catalpol extends lifespan and increases stress tolerance of C. elegans via DAF-16/FOXO and SKN-1/Nrf activation dependent on insulin/IGF signaling and JNK signaling.

  5. Autophagy in C. elegans development.

    Science.gov (United States)

    Palmisano, Nicholas J; Meléndez, Alicia

    2018-04-27

    Autophagy involves the sequestration of cytoplasmic contents in a double-membrane structure referred to as the autophagosome and the degradation of its contents upon delivery to lysosomes. Autophagy activity has a role in multiple biological processes during the development of the nematode Caenorhabditis elegans. Basal levels of autophagy are required to remove aggregate prone proteins, paternal mitochondria, and spermatid-specific membranous organelles. During larval development, autophagy is required for the remodeling that occurs during dauer development, and autophagy can selectively degrade components of the miRNA-induced silencing complex, and modulate miRNA-mediated silencing. Basal levels of autophagy are important in synapse formation and in the germ line, to promote the proliferation of proliferating stem cells. Autophagy activity is also required for the efficient removal of apoptotic cell corpses by promoting phagosome maturation. Finally, autophagy is also involved in lipid homeostasis and in the aging process. In this review, we first describe the molecular complexes involved in the process of autophagy, its regulation, and mechanisms for cargo recognition. In the second section, we discuss the developmental contexts where autophagy has been shown to be important. Studies in C. elegans provide valuable insights into the physiological relevance of this process during metazoan development. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Modeling Complex Systems

    CERN Document Server

    Boccara, Nino

    2010-01-01

    Modeling Complex Systems, 2nd Edition, explores the process of modeling complex systems, providing examples from such diverse fields as ecology, epidemiology, sociology, seismology, and economics. It illustrates how models of complex systems are built and provides indispensable mathematical tools for studying their dynamics. This vital introductory text is useful for advanced undergraduate students in various scientific disciplines, and serves as an important reference book for graduate students and young researchers. This enhanced second edition includes: . -recent research results and bibliographic references -extra footnotes which provide biographical information on cited scientists who have made significant contributions to the field -new and improved worked-out examples to aid a student’s comprehension of the content -exercises to challenge the reader and complement the material Nino Boccara is also the author of Essentials of Mathematica: With Applications to Mathematics and Physics (Springer, 2007).

  7. Modeling Complex Systems

    International Nuclear Information System (INIS)

    Schreckenberg, M

    2004-01-01

    This book by Nino Boccara presents a compilation of model systems commonly termed as 'complex'. It starts with a definition of the systems under consideration and how to build up a model to describe the complex dynamics. The subsequent chapters are devoted to various categories of mean-field type models (differential and recurrence equations, chaos) and of agent-based models (cellular automata, networks and power-law distributions). Each chapter is supplemented by a number of exercises and their solutions. The table of contents looks a little arbitrary but the author took the most prominent model systems investigated over the years (and up until now there has been no unified theory covering the various aspects of complex dynamics). The model systems are explained by looking at a number of applications in various fields. The book is written as a textbook for interested students as well as serving as a comprehensive reference for experts. It is an ideal source for topics to be presented in a lecture on dynamics of complex systems. This is the first book on this 'wide' topic and I have long awaited such a book (in fact I planned to write it myself but this is much better than I could ever have written it!). Only section 6 on cellular automata is a little too limited to the author's point of view and one would have expected more about the famous Domany-Kinzel model (and more accurate citation!). In my opinion this is one of the best textbooks published during the last decade and even experts can learn a lot from it. Hopefully there will be an actualization after, say, five years since this field is growing so quickly. The price is too high for students but this, unfortunately, is the normal case today. Nevertheless I think it will be a great success! (book review)

  8. Modeling the earth system

    Energy Technology Data Exchange (ETDEWEB)

    Ojima, D. [ed.

    1992-12-31

    The 1990 Global Change Institute (GCI) on Earth System Modeling is the third of a series organized by the Office for Interdisciplinary Earth Studies to look in depth at particular issues critical to developing a better understanding of the earth system. The 1990 GCI on Earth System Modeling was organized around three themes: defining critical gaps in the knowledge of the earth system, developing simplified working models, and validating comprehensive system models. This book is divided into three sections that reflect these themes. Each section begins with a set of background papers offering a brief tutorial on the subject, followed by working group reports developed during the institute. These reports summarize the joint ideas and recommendations of the participants and bring to bear the interdisciplinary perspective that imbued the institute. Since the conclusion of the 1990 Global Change Institute, research programs, nationally and internationally, have moved forward to implement a number of the recommendations made at the institute, and many of the participants have maintained collegial interactions to develop research projects addressing the needs identified during the two weeks in Snowmass.

  9. 1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    International Nuclear Information System (INIS)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D.

    2011-01-01

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in 1 H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  10. {sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    Energy Technology Data Exchange (ETDEWEB)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D., E-mail: bernard.lemire@ualberta.ca [University of Alberta, Department of Biochemistry, School of Molecular and Systems Medicine (Canada)

    2011-04-15

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in {sup 1}H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  11. Spaceflight and ageing: reflecting on Caenorhabditis elegans in space.

    Science.gov (United States)

    Honda, Yoko; Honda, Shuji; Narici, Marco; Szewczyk, Nathaniel J

    2014-01-01

    The prospect of space travel continues to capture the imagination. Several competing companies are now promising flights for the general population. Previously, it was recognized that many of the physiological changes that occur with spaceflight are similar to those seen with normal ageing. This led to the notion that spaceflight can be used as a model of accelerated ageing and raised concerns about the safety of individuals engaging in space travel. Paradoxically, however, space travel has been recently shown to be beneficial to some aspects of muscle health in the tiny worm Caenorhabditis elegans. C. elegans is a commonly used laboratory animal for studying ageing. C. elegans displays age-related decline of some biological processes observed in ageing humans, and about 35% of C. elegans' genes have human homologs. Space flown worms were found to have decreased expression of a number of genes that increase lifespan when expressed at lower levels. These changes were accompanied by decreased accumulation of toxic protein aggregates in ageing worms' muscles. Thus, in addition to spaceflight producing physiological changes that are similar to accelerated ageing, it also appears to produce some changes similar to delayed ageing. Here, we put forward the hypothesis that in addition to the previously well-appreciated mechanotransduction changes, neural and endocrine signals are altered in response to spaceflight and that these may have both negative (e.g. less muscle protein) and some positive consequences (e.g. healthier muscles), at least for invertebrates, with respect to health in space. Given that changes in circulating hormones are well documented with age and in astronauts, our view is that further research into the relationship between metabolic control, ageing, and adaptation to the environment should be productive in advancing our understanding of the physiology of both spaceflight and ageing.

  12. Courtship herding in the fiddler crab Uca elegans.

    Science.gov (United States)

    How, Martin J; Hemmi, Jan M

    2008-12-01

    Male and female animals are not always complicit during reproduction, giving rise to coercion. One example of a system that is assumed to involve sexual coercion is the mate herding behaviour of fiddler crabs: males push females towards the home burrow with the goal of forcing copulation at the burrow entrance. We recorded and analysed in detail the courtship behaviour of a North Australian species of fiddler crab Uca elegans. Courtship was composed of four main phases: broadcast waving, outward run, herding and at burrow display. During interactions males produced claw-waving displays which were directed posteriorly towards the female and which varied in timing and structure depending on the courtship phase. We suggest that courtship herding in U. elegans is driven primarily by mate choice for the following reasons, (1) females can evade herding, (2) no other reproductive strategies were observed, (3) males broadcast their presence and accompany courtship with conspicuous claw waves, and (4) the behaviour ends with the female leading the male into the home burrow. As an alternative function for herding in U. elegans we suggest that the behaviour represents a form of courtship guiding, in which males direct complicit females to the correct home burrow.

  13. System equivalent model mixing

    Science.gov (United States)

    Klaassen, Steven W. B.; van der Seijs, Maarten V.; de Klerk, Dennis

    2018-05-01

    This paper introduces SEMM: a method based on Frequency Based Substructuring (FBS) techniques that enables the construction of hybrid dynamic models. With System Equivalent Model Mixing (SEMM) frequency based models, either of numerical or experimental nature, can be mixed to form a hybrid model. This model follows the dynamic behaviour of a predefined weighted master model. A large variety of applications can be thought of, such as the DoF-space expansion of relatively small experimental models using numerical models, or the blending of different models in the frequency spectrum. SEMM is outlined, both mathematically and conceptually, based on a notation commonly used in FBS. A critical physical interpretation of the theory is provided next, along with a comparison to similar techniques; namely DoF expansion techniques. SEMM's concept is further illustrated by means of a numerical example. It will become apparent that the basic method of SEMM has some shortcomings which warrant a few extensions to the method. One of the main applications is tested in a practical case, performed on a validated benchmark structure; it will emphasize the practicality of the method.

  14. Comparison of antibiotic resistance, virulence gene profiles, and pathogenicity of methicillin-resistant and methicillin-susceptible Staphylococcus aureus using a Caenorhabditis elegans infection model

    Science.gov (United States)

    Thompson, Terissa; Brown, Paul D

    2014-01-01

    Objectives: This study compared the presence of 35 virulence genes, resistance phenotypes to 11 anti-staphylococcal antibiotics, and pathogenicity in methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). Methods: Multiplex PCR analysis was used to differentiate Staphylococcus aureus isolates (n = 102) based on characterization of the Staphylococcal Cassette Chromosome mec (SCCmec). Singleplex and multiplex PCR assays targeting 35 virulence determinants were used to analyze the virulence repertoire of S. aureus. In vitro activities of the antibiotics were determined by the disk-diffusion method. The pathogenicity of representative isolates was assessed using Caenorhabditis elegans survival assays. Significance in virulence distribution and antibiotic resistance phenotypes was assessed using the Chi-squared tests. Kaplan–Meier survival estimates were used to analyze nematode survival and significance of survival rates evaluated using the log-rank test. Results: Except for sei (staphylococcal enterotoxin I) (P  =  0.027), all other virulence genes were not significantly associated with MRSA. Resistance to clindamycin (P  =  0.03), tetracycline (P  =  0.048), trimethoprim/sulfamethoxazole (P  =  0.038), and oxacillin (P  =  0.004) was significantly associated with MRSA. Survival assay showed MSSA having a lower median lifespan of 3 days than MRSA that had a median lifespan of 6 days. The difference in the killing time of MRSA and MSSA was significant (P virulence genes. The quicker killing potential of MSSA compared to MRSA suggests that carriage of virulence determinants per se does not determine pathogenicity in S. aureus. Pathogenicity is impacted by other factors, possibly antibiotic resistance. PMID:25319852

  15. Advanced Behavioral Analyses Show that the Presence of Food Causes Subtle Changes in C. elegans Movement.

    Science.gov (United States)

    Angstman, Nicholas B; Frank, Hans-Georg; Schmitz, Christoph

    2016-01-01

    As a widely used and studied model organism, Caenorhabditis elegans worms offer the ability to investigate implications of behavioral change. Although, investigation of C. elegans behavioral traits has been shown, analysis is often narrowed down to measurements based off a single point, and thus cannot pick up on subtle behavioral and morphological changes. In the present study videos were captured of four different C. elegans strains grown in liquid cultures and transferred to NGM-agar plates with an E. coli lawn or with no lawn. Using an advanced software, WormLab, the full skeleton and outline of worms were tracked to determine whether the presence of food affects behavioral traits. In all seven investigated parameters, statistically significant differences were found in worm behavior between those moving on NGM-agar plates with an E. coli lawn and NGM-agar plates with no lawn. Furthermore, multiple test groups showed differences in interaction between variables as the parameters that significantly correlated statistically with speed of locomotion varied. In the present study, we demonstrate the validity of a model to analyze C. elegans behavior beyond simple speed of locomotion. The need to account for a nested design while performing statistical analyses in similar studies is also demonstrated. With extended analyses, C. elegans behavioral change can be investigated with greater sensitivity, which could have wide utility in fields such as, but not limited to, toxicology, drug discovery, and RNAi screening.

  16. Advanced behavioral analyses show that the presence of food causes subtle changes in C. elegans movement

    Directory of Open Access Journals (Sweden)

    Nicholas eAngstman

    2016-03-01

    Full Text Available As a widely used and studied model organism, C. elegans worms offer the ability to investigate implications of behavioral change. Although investigation of C. elegans behavioral traits has been shown, analysis is often narrowed down to measurements based off a single point, and thus cannot pick up on subtle behavioral and morphological changes. In the present study videos were captured of four different C. elegans strains grown in liquid cultures and transferred to NGM-agar plates with an E. coli lawn or with no lawn. Using an advanced software, WormLab, the full skeleton and outline of worms were tracked to determine whether the presence of food affects behavioral traits. In all seven investigated parameters, statistically significant differences were found in worm behavior between those moving on NGM-agar plates with an E. coli lawn and NGM-agar plates with no lawn. Furthermore, multiple test groups showed differences in interaction between variables as the parameters that significantly correlated statistically with speed of locomotion varied. In the present study, we demonstrate the validity of a model to analyze C. elegans behavior beyond simple speed of locomotion. The need to account for a nested design while performing statistical analyses in similar studies is also demonstrated. With extended analyses, C. elegans behavioral change can be investigated with greater sensitivity, which could have wide utility in fields such as, but not limited to, toxicology, drug discovery, and RNAi screening.

  17. A heritable antiviral RNAi response limits Orsay virus infection in Caenorhabditis elegans N2.

    Directory of Open Access Journals (Sweden)

    Mark G Sterken

    Full Text Available Orsay virus (OrV is the first virus known to be able to complete a full infection cycle in the model nematode species Caenorhabditis elegans. OrV is transmitted horizontally and its infection is limited by antiviral RNA interference (RNAi. However, we have no insight into the kinetics of OrV replication in C. elegans. We developed an assay that infects worms in liquid, allowing precise monitoring of the infection. The assay revealed a dual role for the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it limits the progression of the initial infection at the step of recognition of dsRNA. Secondly, it provides an inherited protection against infection in the offspring. This establishes the heritable RNAi response as anti-viral mechanism during OrV infections in C. elegans. Our results further illustrate that the inheritance of the anti-viral response is important in controlling the infection in the canonical wild type Bristol N2. The OrV replication kinetics were established throughout the worm life-cycle, setting a standard for further quantitative assays with the OrV-C. elegans infection model.

  18. Forward and reverse mutagenesis in C. elegans

    Science.gov (United States)

    Kutscher, Lena M.; Shaham, Shai

    2014-01-01

    Mutagenesis drives natural selection. In the lab, mutations allow gene function to be deciphered. C. elegans is highly amendable to functional genetics because of its short generation time, ease of use, and wealth of available gene-alteration techniques. Here we provide an overview of historical and contemporary methods for mutagenesis in C. elegans, and discuss principles and strategies for forward (genome-wide mutagenesis) and reverse (target-selected and gene-specific mutagenesis) genetic studies in this animal. PMID:24449699

  19. Steroid signaling system responds differently to temperature and hormone manipulation in the red-eared slider turtle (Trachemys scripta elegans), a reptile with temperature-dependent sex determination.

    Science.gov (United States)

    Ramsey, M; Crews, D

    2007-01-01

    Many reptiles, including the red-eared slider turtle (Trachemys scripta elegans), exhibit temperature-dependent sex determination (TSD). Temperature determines gonadal sex during the middle of embryogenesis, or the temperature-sensitive period (TSP), when gonadal sex is labile to both temperature and hormones--particularly estrogen. The biological actions of steroid hormones are mediated by their receptors as defined here as the classic transcriptional regulation of target genes. To elucidate estrogen action during sex determination, we examined estrogen receptor alpha (Esr1, hereafter referred to as ERalpha), estrogen receptor beta (Esr2, hereafter referred to as ERbeta), and androgen receptor (Ar, hereafter referred to as AR) expression in slider turtle gonads before, during and after the TSP, as well as following sex reversal via temperature or steroid hormone manipulation. ERalpha and AR levels spike at the female-producing temperature while ovarian sex is determined, but none of the receptors exhibited sexually dimorphic localization within the gonad prior to morphological differentiation. All three receptors respond differentially to sex-reversing treatments. When shifted to female-producing temperatures, embryos maintain ERalpha and AR expression while ERbeta is reduced. When shifted to male-producing temperatures, medullary expression of all three receptors is reduced. Feminization via estradiol (E(2)) treatment at a male-producing temperature profoundly changed the expression patterns for all three receptors. ERalpha and ERbeta redirected to the cortex in E(2)-created ovaries, while AR medullary expression was transiently reduced. Although warmer incubation temperature and estrogen result in the same endpoint (ovarian development), our results indicate different steroid signaling patterns between temperature- and estrogen-induced feminization. 2007 S. Karger AG, Basel

  20. Effects of Genetic Mutations and Chemical Exposures on Caenorhabditis elegans Feeding: Evaluation of a Novel, High-Throughput Screening Assay

    OpenAIRE

    Boyd, Windy A.; McBride, Sandra J.; Freedman, Jonathan H.

    2007-01-01

    Background Government agencies have defined a need to reduce, refine or replace current mammalian-based bioassays with testing methods that use alternative species. Invertebrate species, such as Caenorhabditis elegans, provide an attractive option because of their short life cycles, inexpensive maintenance, and high degree of evolutionary conservation with higher eukaryotes. The C. elegans pharynx is a favorable model for studying neuromuscular function, and the effects of chemicals on neurom...

  1. Life cycle and population growth rate of Caenorhabditis elegans studied by a new method

    OpenAIRE

    Schroeder Fabian; Muschiol Daniel; Traunspurger Walter

    2009-01-01

    Abstract Background The free-living nematode Caenorhabditis elegans is the predominant model organism in biological research, being used by a huge number of laboratories worldwide. Many researchers have evaluated life-history traits of C. elegans in investigations covering quite different aspects such as ecotoxicology, inbreeding depression and heterosis, dietary restriction/supplement, mutations, and ageing. Such traits include juvenile growth rates, age at sexual maturity, adult body size, ...

  2. High-throughput screen for novel antimicrobials using a whole animal infection model.

    Science.gov (United States)

    Moy, Terence I; Conery, Annie L; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E; Ausubel, Frederick M

    2009-07-17

    The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen. Here, we describe an automated, high-throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. Using a robot to dispense live, infected animals into 384-well plates and automated microscopy and image analysis, we identified 28 compounds and extracts not previously reported to have antimicrobial properties, including six structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use.

  3. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2009-01-01

    This third volume completes the Work Mechanical Systems, Classical Models. The first two volumes dealt with particle dynamics and with discrete and continuous mechanical systems. The present volume studies analytical mechanics. Topics like Lagrangian and Hamiltonian mechanics, the Hamilton-Jacobi method, and a study of systems with separate variables are thoroughly discussed. Also included are variational principles and canonical transformations, integral invariants and exterior differential calculus, and particular attention is given to non-holonomic mechanical systems. The author explains in detail all important aspects of the science of mechanics, regarded as a natural science, and shows how they are useful in understanding important natural phenomena and solving problems of interest in applied and engineering sciences. Professor Teodorescu has spent more than fifty years as a Professor of Mechanics at the University of Bucharest and this book relies on the extensive literature on the subject as well as th...

  4. Selective visualization of fluorescent sterols in Caenorhabditis elegans by bleach-rate-based image segmentation

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Landt Larsen, Ane; Færgeman, Nils J.

    2010-01-01

    The nematode Caenorhabditis elegans is a genetically tractable model organism to investigate sterol transport. In vivo imaging of the fluorescent sterol, dehydroergosterol (DHE), is challenged by C. elegans' high autofluorescence in the same spectral region as emission of DHE. We present a method....... Bleach-rate constants were determined for DHE in vivo and confirmed in model membranes. Using this method, we could detect enrichment of DHE in specific tissues like the nerve ring, the spermateca and oocytes. We confirm these results in C. elegans gut-granule-loss (glo) mutants with reduced...... homologues of Niemann-Pick C disease proteins. Our approach is generally useful for identifying fluorescent probes in the presence of high cellular autofluorescence....

  5. Optogenetic mutagenesis in Caenorhabditis elegans.

    Science.gov (United States)

    Noma, Kentaro; Jin, Yishi

    2015-12-03

    Reactive oxygen species (ROS) can modify and damage DNA. Here we report an optogenetic mutagenesis approach that is free of toxic chemicals and easy to perform by taking advantage of a genetically encoded ROS generator. This method relies on the potency of ROS generation by His-mSOG, the mini singlet oxygen generator, miniSOG, fused to a histone. Caenorhabditis elegans expressing His-mSOG in the germline behave and reproduce normally, without photoinduction. Following exposure to blue light, the His-mSOG animals produce progeny with a wide range of heritable phenotypes. We show that optogenetic mutagenesis by His-mSOG induces a broad spectrum of mutations including single-nucleotide variants (SNVs), chromosomal deletions, as well as integration of extrachromosomal transgenes, which complements those derived from traditional chemical or radiation mutagenesis. The optogenetic mutagenesis expands the toolbox for forward genetic screening and also provides direct evidence that nuclear ROS can induce heritable and specific genetic mutations.

  6. Modern techniques for the analysis of chromatin and nuclear organization in C. elegans.

    Science.gov (United States)

    Askjaer, Peter; Ercan, Sevinç; Meister, Peter

    2014-04-02

    In recent years, Caenorhabditis elegans has emerged as a new model to investigate the relationships between nuclear architecture, cellular differentiation, and organismal development. On one hand, C. elegans with its fixed lineage and transparent body is a great model organism to observe gene functions in vivo in specific cell types using microscopy. On the other hand, two different techniques have been applied in nematodes to identify binding sites for chromatin-associated proteins genome-wide: chromatin immunoprecipitation (ChIP), and Dam-mediated identification (DamID). We summarize here all three techniques together as they are complementary. We also highlight strengths and differences of the individual approaches.

  7. Modeling dental radiographic systems

    International Nuclear Information System (INIS)

    Webber, R.L.

    1980-01-01

    The Bureau of Radiological Health has been actively collaborating with the Clinical Investigations Branch, NIDR, in applied research involving diagnostic use of ionizing radiation in dentistry. This work has centered on the search for alternatives to conventional radiographic systems in an attempt to improve diagnostic performance while reducing the required exposure. The basic approach involves analysis of factors limiting performance of properly defined diagnostic tasks and the modeling alternative systems with an eye toward increasing objective measures of performance. Previous collaborative work involved using a nonlinear model to compare various x-ray spectra. The data were expressed as brightness-contrast versus exposure for simulated tasks of clinical interest. This report supplements these findings by extending the number of parameters under investigation and modifying the mode of data display so that an actual radiographic image can be simulated on a television screen

  8. The nongenotoxic carcinogens naphthalene and para-dichlorobenzene suppress apoptosis in Caenorhabditis elegans.

    Science.gov (United States)

    Kokel, David; Li, Yehua; Qin, Jun; Xue, Ding

    2006-06-01

    Naphthalene (1) and para-dichlorobenzene (PDCB, 2), which are widely used as moth repellents and air fresheners, cause cancer in rodents and are potential human carcinogens. However, their mechanisms of action remain unclear. Here we describe a novel method for delivering and screening hydrophobic chemicals in C. elegans and apply this technique to investigate the ways in which naphthalene and PDCB may promote tumorigenesis in mammals. We show that naphthalene and PDCB inhibit apoptosis in C. elegans, a result that suggests a cellular mechanism by which these chemicals may promote the survival and proliferation of latent tumor cells. In addition, we find that a naphthalene metabolite directly inactivates caspases by oxidizing the active site cysteine residue; this suggests a molecular mechanism by which these chemicals suppress apoptosis. Naphthalene and PDCB are the first small-molecule apoptosis inhibitors identified in C. elegans. The power of C. elegans molecular genetics, in combination with the possibility of carrying out large-scale chemical screens in this organism, makes C. elegans an attractive and economic animal model for both toxicological studies and drug screens.

  9. SRP-2 is a cross-class inhibitor that participates in postembryonic development of the nematode Caenorhabditis elegans: initial characterization of the clade L serpins.

    Science.gov (United States)

    Pak, Stephen C; Kumar, Vasantha; Tsu, Christopher; Luke, Cliff J; Askew, Yuko S; Askew, David J; Mills, David R; Brömme, Dieter; Silverman, Gary A

    2004-04-09

    High molecular weight serpins are members of a large superfamily of structurally conserved proteins that inactivate target proteinases by a suicide substrate-like mechanism. In vertebrates, different clades of serpins distribute predominantly to either the intracellular or extracellular space. Although much is known about the function, structure, and inhibitory mechanism of circulating serpins such as alpha(1)-antitrypsin (SERPINA1) and antithrombin III (SERPINC1), relatively little is known about the function of the vertebrate intracellular (clade B) serpins. To gain a better understanding of the biology of the intracellular serpins, we initiated a comparative genomics study using Caenorhabditis elegans as a model system. A screen of the C. elegans genomic and cDNA databases revealed nine serpin genes, tandemly arrayed on chromosome V. Although the C. elegans serpins represent a unique clade (L), they share significant functional homology with members of the clade B group of intracellular serpins, since they lack typical N-terminal signal peptides and reside intracellularly. To determine whether nematode serpins function as proteinase inhibitors, one family member, srp-2, was chosen for further characterization. Biochemical analysis of recombinant SRP-2 protein revealed SRP-2 to be a dual cross-class inhibitor of the apoptosis-related serine proteinase, granzyme B, and the lysosomal cysteine proteinases, cathepsins K, L, S, and V. Analysis of temporal and spatial expression indicated that SRP-2 was present during early embryonic development and highly expressed in the intestine and hypoderm of larval and adult worms. Transgenic animals engineered to overexpress SRP-2 were slow growing and/or arrested at the first, second, or third larval stages. These data suggest that perturbations of serpin-proteinase balance are critical for correct postembryonic development in C. elegans.

  10. Modeling Novo Nordisk Production Systems

    DEFF Research Database (Denmark)

    Miller, Thomas Dedenroth

    1997-01-01

    This report describes attributes of models and systems, and how models can be used for description of production systems. There are special attention on the 'Theory of Domains'.......This report describes attributes of models and systems, and how models can be used for description of production systems. There are special attention on the 'Theory of Domains'....

  11. Establishing in vitro Zinnia elegans cell suspension culture with high tracheary elements differentiation

    NARCIS (Netherlands)

    Twumasi, P.; Schel, J.H.N.; Ieperen, van W.; Woltering, E.J.; Emons, A.M.C.

    2009-01-01

    The Zinnia elegans mesophyll cell culture is a useful system for xylogenesis studies. The system is associated with highly synchronous tracheary element (TE) differentiation, making it more suitable for molecular studies requiring larger amounts of molecular isolates, such as mRNA and proteins and

  12. Combination therapy with thioridazine and dicloxacillin combats meticillin-resistant Staphylococcus aureus infection in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Poulsen, Marianne Ø; Schøler, Lone; Nielsen, Anette

    2014-01-01

    the thresholds of toxicity, determined by larval development, and induction of stress-response markers. No measurable effects were seen at concentrations of less than 64 mg TZ l(-1). Seven different MRSA strains were tested for pathogenicity against C. elegans, and the most virulent strain (ATCC 33591......) was selected for further analyses. In a final experiment, full-grown C. elegans were exposed to the test strain for 3 days and subsequently treated with 8 mg DCX l(-1) and 8 mg TZ l(-1) for 2 days. This resulted in a 14-fold reduction in the intestinal MRSA load as compared with untreated controls. Each drug...... alone resulted in a two- to threefold reduction in MRSA load. In conclusion, C. elegans can be used as a simple model to test synergy between DCX and TZ against MRSA. The previously demonstrated in vitro synergy can be reproduced in vivo....

  13. Combination therapy with thioridazine and dicloxacillin combats methicillin-resistant Staphylococcus aureus infection in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Poulsen, Marianne Østergaard; Schøler, Lone; Nielsen, Anette

    2014-01-01

    the thresholds of toxicity, determined by larval development, and induction of stress-response markers. No measurable effects were seen at concentrations of less than 64 mg TZ l(-1). Seven different MRSA strains were tested for pathogenicity against C. elegans, and the most virulent strain (ATCC 33591......) was selected for further analyses. In a final experiment, full-grown C. elegans were exposed to the test strain for 3 days and subsequently treated with 8 mg DCX l(-1) and 8 mg TZ l(-1) for 2 days. This resulted in a 14-fold reduction in the intestinal MRSA load as compared with untreated controls. Each drug...... alone resulted in a two- to threefold reduction in MRSA load. In conclusion, C. elegans can be used as a simple model to test synergy between DCX and TZ against MRSA. The previously demonstrated in vitro synergy can be reproduced in vivo....

  14. Undulatory locomotion of finite filaments: lessons from Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Berman, R S; Kenneth, O; Sznitman, J; Leshansky, A M

    2013-01-01

    Undulatory swimming is a widespread propulsion strategy adopted by many small-scale organisms including various single-cell eukaryotes and nematodes. In this work, we report a comprehensive study of undulatory locomotion of a finite filament using (i) approximate resistive force theory (RFT) assuming a local nature of hydrodynamic interaction between the filament and the surrounding viscous liquid and (ii) particle-based numerical computations taking into account the intra-filament hydrodynamic interaction. Using the ubiquitous model of a propagating sinusoidal waveform, we identify the limit of applicability of the RFT and determine the optimal propulsion gait in terms of (i) swimming distance per period of undulation and (ii) hydrodynamic propulsion efficiency. The occurrence of the optimal swimming gait maximizing hydrodynamic efficiency at finite wavelength in particle-based computations diverges from the prediction of the RFT. To compare the model swimmer powered by sine wave undulations to biological undulatory swimmers, we apply the particle-based approach to study locomotion of the model organism nematode Caenorhabditis elegans using the swimming gait extracted from experiments. The analysis reveals that even though the amplitude and the wavenumber of undulations are similar to those determined for the best performing sinusoidal swimmer, C. elegans overperforms the latter in terms of both displacement and hydrodynamic efficiency. Further comparison with other undulatory microorganisms reveals that many adopt waveforms with characteristics similar to the optimal model swimmer, yet real swimmers still manage to beat the best performing sine-wave swimmer in terms of distance covered per period. Overall our results underline the importance of further waveform optimization, as periodic undulations adopted by C. elegans and other organisms deviate considerably from a simple sine wave. (paper)

  15. The adiponectin receptor homologs in C. elegans promote energy utilization and homeostasis

    DEFF Research Database (Denmark)

    Svensson, Emma; Olsen, Louise Cathrine Braun; Mörck, Catarina

    2011-01-01

    in the nematode C. elegans, named paqr-1, paqr-2 and paqr-3. These are differently expressed in the intestine (the main fat-storing tissue), hypodermis, muscles, neurons and secretory tissues, from which they could exert systemic effects. Analysis of mutants revealed that paqr-1 and -2 are novel metabolic...... regulators in C. elegans and that they act redundantly but independently from paqr-3. paqr-2 is the most important of the three paqr genes: mutants grow poorly, fail to adapt to growth at low temperature, and have a very high fat content with an abnormal enrichment in long (C20) poly-unsaturated fatty acids...... when combined with the paqr-1 mutation. paqr-2 mutants are also synthetic lethal with mutations in nhr-49, sbp-1 and fat-6, which are C. elegans homologs of nuclear hormone receptors, SREBP and FAT-6 (a Δ9 desaturase), respectively. Like paqr-2, paqr-1 is also synthetic lethal with sbp-1. Mutations...

  16. Control of neuropeptide expression by parallel activity-dependent pathways in caenorhabditis elegans

    DEFF Research Database (Denmark)

    Rojo Romanos, Teresa; Petersen, Jakob Gramstrup; Pocock, Roger

    2017-01-01

    Monitoring of neuronal activity within circuits facilitates integrated responses and rapid changes in behavior. We have identified a system in Caenorhabditis elegans where neuropeptide expression is dependent on the ability of the BAG neurons to sense carbon dioxide. In C. Elegans, CO 2 sensing...... is predominantly coordinated by the BAG-expressed receptor-type guanylate cyclase GCY-9. GCY-9 binding to CO 2 causes accumulation of cyclic GMP and opening of the cGMP-gated TAX-2/TAX-4 cation channels; provoking an integrated downstream cascade that enables C. Elegans to avoid high CO 2. Here we show that c...... that expression of flp-19::GFP is controlled in parallel to GCY-9 by the activity-dependent transcription factor CREB (CRH-1) and the cAMP-dependent protein kinase (KIN-2) signaling pathway. We therefore show that two parallel pathways regulate neuropeptide gene expression in the BAG sensory neurons: the ability...

  17. Analysis of the C. elegans Nucleolus by Immuno-DNA FISH.

    Science.gov (United States)

    Lanctôt, Christian

    2016-01-01

    Caenorhabditis elegans is a well-established model organism which allows, among others, to investigate the link between nucleolar structure/function on the one hand and cell fate choices and cellular differentiation on the other. In addition, C. elegans can be used to study the role of the nucleolus in processes that can be difficult to faithfully reproduce in vitro, such as gametogenesis, disease development, and aging. Here I present two complementary techniques, immunofluorescent staining and DNA fluorescence in situ hybridization, that have been adapted to label nucleolar components at various stages of the life cycle of the worm.

  18. Inhibition of HMG-CoA reductase induces the UPR pathway in C. elegans

    DEFF Research Database (Denmark)

    Elmelund-Præstekær, Louise Cathrine Braun; Hansen, Nadia Jin Storm; Pilon, Marc

    -requiring enzyme-1 (IRE-1), and activating transcription factor-6 (ATF-6). Using a transgenic GFP reporter strain of the model organism C. elegans, we have recently identified that inhibition of the enzyme HMG-CoA reductase (HMG-CoAR) with Fluvastatin and knock down of HMG-CoAR using RNA interference (RNAi) both...... including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) which are necessary for posttranslational prenylation of several small G proteins. C. elegans are cholesterol auxotrophs, which enable us to investigate the isoprenoid branch and its role in UPR induction. We found...

  19. A Multiparameter Network Reveals Extensive Divergence between C. elegans bHLH Transcription Factors

    DEFF Research Database (Denmark)

    Grove, C.; De Masi, Federico; Newburger, Daniel

    2009-01-01

    parameters remain undetermined. We comprehensively identify dimerization partners, spatiotemporal expression patterns, and DNA-binding specificities for the C. elegans bHLH family of TFs, and model these data into an integrated network. This network displays both specificity and promiscuity, as some b......HLH proteins, DNA sequences, and tissues are highly connected, whereas others are not. By comparing all bHLH TFs, we find extensive divergence and that all three parameters contribute equally to bHLH divergence. Our approach provides a framework for examining divergence for other protein families in C. elegans...

  20. Identification of novel protein functions and signaling mechanisms by genetics and quantitative phosphoproteomics in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Fredens, Julius; Engholm-Keller, Kasper; Møller-Jensen, Jakob

    2014-01-01

    knockdown by feeding the nematode on pre-labeled lysine auxotroph Escherichia coli. In this chapter, we describe in details the generation of the E. coli strain, incorporation of heavy isotope-labeled lysine in C. elegans, and the procedure for a comprehensive global phosphoproteomic experiment.......Stable isotope labeling by amino acids combined with mass spectrometry is a widely used methodology for measuring relative changes in protein and phosphorylation levels at a global level. We have applied this method to the model organism Caenorhabditis elegans in combination with RNAi-mediated gene...

  1. Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.

    Science.gov (United States)

    Sarkies, Peter; Ashe, Alyson; Le Pen, Jérémie; McKie, Mikel A; Miska, Eric A

    2013-08-01

    Positive-strand RNA viruses encompass more than one-third of known virus genera and include many medically and agriculturally relevant human, animal, and plant pathogens. The nematode Caenorhabditis elegans and its natural pathogen, the positive-strand RNA virus Orsay, have recently emerged as a new animal model to understand the mechanisms and evolution of innate immune responses. In particular, the RNA interference (RNAi) pathway is required for C. elegans resistance to viral infection. Here we report the first genome-wide analyses of gene expression upon viral infection in C. elegans. Using the laboratory strain N2, we identify a novel C. elegans innate immune response specific to viral infection. A subset of these changes is driven by the RNAi response to the virus, which redirects the Argonaute protein RDE-1 from its endogenous small RNA cofactors, leading to loss of repression of endogenous RDE-1 targets. Additionally, we show that a C. elegans wild isolate, JU1580, has a distinct gene expression signature in response to viral infection. This is associated with a reduction in microRNA (miRNA) levels and an up-regulation of their target genes. Intriguingly, alterations in miRNA levels upon JU1580 infection are associated with a transformation of the antiviral transcriptional response into an antibacterial-like response. Together our data support a model whereby antiviral RNAi competes with endogenous small RNA pathways, causing widespread transcriptional changes. This provides an elegant mechanism for C. elegans to orchestrate its antiviral response, which may have significance for the relationship between small RNA pathways and immune regulation in other organisms.

  2. Cell Death in C. elegans Development.

    Science.gov (United States)

    Malin, Jennifer Zuckerman; Shaham, Shai

    2015-01-01

    Cell death is a common and important feature of animal development, and cell death defects underlie many human disease states. The nematode Caenorhabditis elegans has proven fertile ground for uncovering molecular and cellular processes controlling programmed cell death. A core pathway consisting of the conserved proteins EGL-1/BH3-only, CED-9/BCL2, CED-4/APAF1, and CED-3/caspase promotes most cell death in the nematode, and a conserved set of proteins ensures the engulfment and degradation of dying cells. Multiple regulatory pathways control cell death onset in C. elegans, and many reveal similarities with tumor formation pathways in mammals, supporting the idea that cell death plays key roles in malignant progression. Nonetheless, a number of observations suggest that our understanding of developmental cell death in C. elegans is incomplete. The interaction between dying and engulfing cells seems to be more complex than originally appreciated, and it appears that key aspects of cell death initiation are not fully understood. It has also become apparent that the conserved apoptotic pathway is dispensable for the demise of the C. elegans linker cell, leading to the discovery of a previously unexplored gene program promoting cell death. Here, we review studies that formed the foundation of cell death research in C. elegans and describe new observations that expand, and in some cases remodel, this edifice. We raise the possibility that, in some cells, more than one death program may be needed to ensure cell death fidelity. © 2015 Elsevier Inc. All rights reserved.

  3. Fourier-Based Diffraction Analysis of Live Caenorhabditis elegans.

    Science.gov (United States)

    Magnes, Jenny; Hastings, Harold M; Raley-Susman, Kathleen M; Alivisatos, Clara; Warner, Adam; Hulsey-Vincent, Miranda

    2017-09-13

    This manuscript describes how to classify nematodes using temporal far-field diffraction signatures. A single C. elegans is suspended in a water column inside an optical cuvette. A 632 nm continuous wave HeNe laser is directed through the cuvette using front surface mirrors. A significant distance of at least 20-30 cm traveled after the light passes through the cuvette ensures a useful far-field (Fraunhofer) diffraction pattern. The diffraction pattern changes in real time as the nematode swims within the laser beam. The photodiode is placed off-center in the diffraction pattern. The voltage signal from the photodiode is observed in real time and recorded using a digital oscilloscope. This process is repeated for 139 wild type and 108 "roller" C. elegans. Wild type worms exhibit a rapid oscillation pattern in solution. The "roller" worms have a mutation in a key component of the cuticle that interferes with smooth locomotion. Time intervals that are not free of saturation and inactivity are discarded. It is practical to divide each average by its maximum to compare relative intensities. The signal for each worm is Fourier transformed so that the frequency pattern for each worm emerges. The signal for each type of worm is averaged. The averaged Fourier spectra for the wild type and the "roller" C. elegans are distinctly different and reveal that the dynamic worm shapes of the two different worm strains can be distinguished using Fourier analysis. The Fourier spectra of each worm strain match an approximate model using two different binary worm shapes that correspond to locomotory moments. The envelope of the averaged frequency distribution for actual and modeled worms confirms the model matches the data. This method can serve as a baseline for Fourier analysis for many microscopic species, as every microorganism will have its unique Fourier spectrum.

  4. Bacillus licheniformis Isolated from Traditional Korean Food Resources Enhances the Longevity of Caenorhabditis elegans through Serotonin Signaling.

    Science.gov (United States)

    Park, Mi Ri; Oh, Sangnam; Son, Seok Jun; Park, Dong-June; Oh, Sejong; Kim, Sae Hun; Jeong, Do-Youn; Oh, Nam Su; Lee, Youngbok; Song, Minho; Kim, Younghoon

    2015-12-02

    In this study, we investigated potentially probiotic Bacillus licheniformis strains isolated from traditional Korean food sources for ability to enhance longevity using the nematode Caenorhabditis elegans as a simple in vivo animal model. We first investigated whether B. licheniformis strains were capable of modulating the lifespan of C. elegans. Among the tested strains, preconditioning with four B. licheniformis strains significantly enhanced the longevity of C. elegans. Unexpectedly, plate counting and transmission electron microscopy (TEM) results indicated that B. licheniformis strains were not more highly attached to the C. elegans intestine compared with Escherichia coli OP50 or Lactobacillus rhamnosus GG controls. In addition, qRT-PCR and an aging assay with mutant worms showed that the conditioning of B. licheniformis strain 141 directly influenced genes associated with serotonin signaling in nematodes, including tph-1 (tryptophan hydroxylase), bas-1 (serotonin- and dopamine-synthetic aromatic amino acid decarboxylase), mod-1 (serotonin-gated chloride channel), ser-1, and ser-7 (serotonin receptors) during C. elegans aging. Our findings suggest that B. licheniformis strain 141, which is isolated from traditional Korean foods, is a probiotic generally recognized as safe (GRAS) strain that enhances the lifespan of C. elegans via host serotonin signaling.

  5. An update on the use of C. elegans for preclinical drug discovery: screening and identifying anti-infective drugs.

    Science.gov (United States)

    Kim, Wooseong; Hendricks, Gabriel Lambert; Lee, Kiho; Mylonakis, Eleftherios

    2017-06-01

    The emergence of antibiotic-resistant and -tolerant bacteria is a major threat to human health. Although efforts for drug discovery are ongoing, conventional bacteria-centered screening strategies have thus far failed to yield new classes of effective antibiotics. Therefore, new paradigms for discovering novel antibiotics are of critical importance. Caenorhabditis elegans, a model organism used for in vivo, offers a promising solution for identification of anti-infective compounds. Areas covered: This review examines the advantages of C. elegans-based high-throughput screening over conventional, bacteria-centered in vitro screens. It discusses major anti-infective compounds identified from large-scale C. elegans-based screens and presents the first clinically-approved drugs, then known bioactive compounds, and finally novel small molecules. Expert opinion: There are clear advantages of using a C. elegans-infection based screening method. A C. elegans-based screen produces an enriched pool of non-toxic, efficacious, potential anti-infectives, covering: conventional antimicrobial agents, immunomodulators, and anti-virulence agents. Although C. elegans-based screens do not denote the mode of action of hit compounds, this can be elucidated in secondary studies by comparing the results to target-based screens, or conducting subsequent target-based screens, including the genetic knock-down of host or bacterial genes.

  6. Microfluidic Device to Measure the Speed of C. elegans Using the Resistance Change of the Flexible Electrode

    Directory of Open Access Journals (Sweden)

    Jaehoon Jung

    2016-03-01

    Full Text Available This work presents a novel method to assess the condition of Caenorhabditis elegans (C. elegans through a resistance measurement of its undulatory locomotion speed inside a micro channel. As the worm moves over the electrode inside the micro channel, the length of the electrode changes, consequently behaving like a strain gauge. In this paper, the electrotaxis was applied for controlling the direction of motion of C. elegans as an external stimulus, resulting in the worm moving towards the cathode of the circuit. To confirm the proposed measurement method, a microfluidic device was developed that employs a sinusoidal channel and a thin polydimethylsiloxane (PDMS layer with an electrode. The PDMS layer maintains a porous structure to enable the flexibility of the electrode. In this study, 6 measurements were performed to obtain the speed of an early adult stage C. elegans, where the measured average speed was 0.35 (±0.05 mm/s. The results of this work demonstrate the application of our method to measure the speed of C. elegans undulatory locomotion. This novel approach can be applied to make such measurements without an imaging system, and more importantly, allows directly to detect the locomotion of C. elegans using an electrical signal (i.e., the change in resistance.

  7. Google matrix analysis of C.elegans neural network

    Energy Technology Data Exchange (ETDEWEB)

    Kandiah, V., E-mail: kandiah@irsamc.ups-tlse.fr; Shepelyansky, D.L., E-mail: dima@irsamc.ups-tlse.fr

    2014-05-01

    We study the structural properties of the neural network of the C.elegans (worm) from a directed graph point of view. The Google matrix analysis is used to characterize the neuron connectivity structure and node classifications are discussed and compared with physiological properties of the cells. Our results are obtained by a proper definition of neural directed network and subsequent eigenvector analysis which recovers some results of previous studies. Our analysis highlights particular sets of important neurons constituting the core of the neural system. The applications of PageRank, CheiRank and ImpactRank to characterization of interdependency of neurons are discussed.

  8. Google matrix analysis of C.elegans neural network

    International Nuclear Information System (INIS)

    Kandiah, V.; Shepelyansky, D.L.

    2014-01-01

    We study the structural properties of the neural network of the C.elegans (worm) from a directed graph point of view. The Google matrix analysis is used to characterize the neuron connectivity structure and node classifications are discussed and compared with physiological properties of the cells. Our results are obtained by a proper definition of neural directed network and subsequent eigenvector analysis which recovers some results of previous studies. Our analysis highlights particular sets of important neurons constituting the core of the neural system. The applications of PageRank, CheiRank and ImpactRank to characterization of interdependency of neurons are discussed.

  9. Laterally orienting C. elegans using geometry at microscale for high-throughput visual screens in neurodegeneration and neuronal development studies.

    Directory of Open Access Journals (Sweden)

    Ivan de Carlos Cáceres

    Full Text Available C. elegans is an excellent model system for studying neuroscience using genetics because of its relatively simple nervous system, sequenced genome, and the availability of a large number of transgenic and mutant strains. Recently, microfluidic devices have been used for high-throughput genetic screens, replacing traditional methods of manually handling C. elegans. However, the orientation of nematodes within microfluidic devices is random and often not conducive to inspection, hindering visual analysis and overall throughput. In addition, while previous studies have utilized methods to bias head and tail orientation, none of the existing techniques allow for orientation along the dorso-ventral body axis. Here, we present the design of a simple and robust method for passively orienting worms into lateral body positions in microfluidic devices to facilitate inspection of morphological features with specific dorso-ventral alignments. Using this technique, we can position animals into lateral orientations with up to 84% efficiency, compared to 21% using existing methods. We isolated six mutants with neuronal development or neurodegenerative defects, showing that our technology can be used for on-chip analysis and high-throughput visual screens.

  10. A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-associated degradation in C. elegans.

    Directory of Open Access Journals (Sweden)

    Mark T Miedel

    Full Text Available Endoplasmic-reticulum associated degradation (ERAD is a major cellular misfolded protein disposal pathway that is well conserved from yeast to mammals. In yeast, a mutant of carboxypeptidase Y (CPY* was found to be a luminal ER substrate and has served as a useful marker to help identify modifiers of the ERAD pathway. Due to its ease of genetic manipulation and the ability to conduct a genome wide screen for modifiers of molecular pathways, C. elegans has become one of the preferred metazoans for studying cell biological processes, such as ERAD. However, a marker of ERAD activity comparable to CPY* has not been developed for this model system. We describe a mutant of pro-cathepsin L fused to YFP that no longer targets to the lysosome, but is efficiently eliminated by the ERAD pathway. Using this mutant pro-cathepsin L, we found that components of the mammalian ERAD system that participate in the degradation of ER luminal substrates were conserved in C. elegans. This transgenic line will facilitate high-throughput genetic or pharmacological screens for ERAD modifiers using widefield epifluorescence microscopy.

  11. Angiostrongylus cantonensis daf-2 regulates dauer, longevity and stress in Caenorhabditis elegans.

    Science.gov (United States)

    Yan, Baolong; Sun, Weiwei; Shi, Xiaomeng; Huang, Liyang; Chen, Lingzi; Wang, Suhua; Yan, Lanzhu; Liang, Shaohui; Huang, Huicong

    2017-06-15

    The insulin-like signaling (IIS) pathway is considered to be significant in regulating fat metabolism, dauer formation, stress response and longevity in Caenorhabditis elegans. "Dauer hypothesis" indicates that similar IIS transduction mechanism regulates dauer development in free-living nematode C. elegans and the development of infective third-stage larvae (iL3) in parasitic nematodes, and this is bolstered by a few researches on structures and functions of the homologous genes in the IIS pathway cloned from several parasitic nematodes. In this study, we identified the insulin-like receptor encoding gene, Acan-daf-2, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. The sequence of Acan-DAF-2, consisting of 1413 amino acids, contained all of the characteristic domains of insulin-like receptors from other taxa. The expression patterns of Acan-daf-2 in the C. elegans surrogate system showed that pAcan-daf-2:gfp was only expressed in intestine, compared with the orthologue in C. elegans, Ce-daf-2 in both intestine and neurons. In addition to the similar genomic organization to Ce-daf-2, Acan-DAF-2 could also negatively regulate Ce-DAF-16A through nuclear/cytosolic translocation and partially restore the C. elegans daf-2(e1370) mutation in longevity, dauer formation and stress resistance. These findings provided further evidence of the functional conservation of DAF-2 between parasitic nematodes and the free-living nematode C. elegans, and might be significant in understanding the developmental biology of nematode parasites, particularly in the infective process and the host-specificity. Copyright © 2017. Published by Elsevier B.V.

  12. Inactivity periods and postural change speed can explain atypical postural change patterns of Caenorhabditis elegans mutants.

    Science.gov (United States)

    Fukunaga, Tsukasa; Iwasaki, Wataru

    2017-01-19

    With rapid advances in genome sequencing and editing technologies, systematic and quantitative analysis of animal behavior is expected to be another key to facilitating data-driven behavioral genetics. The nematode Caenorhabditis elegans is a model organism in this field. Several video-tracking systems are available for automatically recording behavioral data for the nematode, but computational methods for analyzing these data are still under development. In this study, we applied the Gaussian mixture model-based binning method to time-series postural data for 322 C. elegans strains. We revealed that the occurrence patterns of the postural states and the transition patterns among these states have a relationship as expected, and such a relationship must be taken into account to identify strains with atypical behaviors that are different from those of wild type. Based on this observation, we identified several strains that exhibit atypical transition patterns that cannot be fully explained by their occurrence patterns of postural states. Surprisingly, we found that two simple factors-overall acceleration of postural movement and elimination of inactivity periods-explained the behavioral characteristics of strains with very atypical transition patterns; therefore, computational analysis of animal behavior must be accompanied by evaluation of the effects of these simple factors. Finally, we found that the npr-1 and npr-3 mutants have similar behavioral patterns that were not predictable by sequence homology, proving that our data-driven approach can reveal the functions of genes that have not yet been characterized. We propose that elimination of inactivity periods and overall acceleration of postural change speed can explain behavioral phenotypes of strains with very atypical postural transition patterns. Our methods and results constitute guidelines for effectively finding strains that show "truly" interesting behaviors and systematically uncovering novel gene

  13. From the Cover: Harmane-Induced Selective Dopaminergic Neurotoxicity in Caenorhabditis elegans.

    Science.gov (United States)

    Sammi, Shreesh Raj; Agim, Zeynep Sena; Cannon, Jason R

    2018-02-01

    Parkinson's disease (PD) is a debilitating neurodegenerative disease. Although numerous exposures have been linked to PD etiology, causative factors for most cases remain largely unknown. Emerging data on the neurotoxicity of heterocyclic amines suggest that this class of compounds should be examined for relevance to PD. Here, using Caenorhabditis elegans as a model system, we tested whether harmane exposure produced selective toxicity to dopamine neurons that is potentially relevant to PD. Harmane is a known tremorigenic β-carboline (a type of heterocyclic amine) found in cooked meat, roasted coffee beans, and tobacco. Thus, this compound represents a potentially important exposure. In the nematode model, we observed dopaminergic neurons to be selectively vulnerable, showing significant loss in terms of structure and function at lower doses than other neuronal populations. In examining mechanisms of toxicity, we observed significant harmane-induced decreases in mitochondrial viability and increased reactive oxygen species levels. Blocking transport through the dopamine transporter (DAT) was not neuroprotective, suggesting that harmane is unlikely to enter the cell through DAT. However, a mitochondrial complex I activator did partially ameliorate neurodegeneration. Further, mitochondrial complex I activator treatment reduced harmane-induced dopamine depletion, measured by the 1-nonanol assay. In summary, we have shown that harmane exposure in C. elegans produces selective dopaminergic neurotoxicity that may bear relevance to PD, and that neurotoxicity may be mediated through mitochondrial mechanisms. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans.

    Science.gov (United States)

    Hussey, Rosalind; Stieglitz, Jon; Mesgarzadeh, Jaleh; Locke, Tiffany T; Zhang, Ying K; Schroeder, Frank C; Srinivasan, Supriya

    2017-05-01

    It is now established that the central nervous system plays an important role in regulating whole body metabolism and energy balance. However, the extent to which sensory systems relay environmental information to modulate metabolic events in peripheral tissues has remained poorly understood. In addition, it has been challenging to map the molecular mechanisms underlying discrete sensory modalities with respect to their role in lipid metabolism. In previous work our lab has identified instructive roles for serotonin signaling as a surrogate for food availability, as well as oxygen sensing, in the control of whole body metabolism. In this study, we now identify a role for a pair of pheromone-sensing neurons in regulating fat metabolism in C. elegans, which has emerged as a tractable and highly informative model to study the neurobiology of metabolism. A genetic screen revealed that GPA-3, a member of the Gα family of G proteins, regulates body fat content in the intestine, the major metabolic organ for C. elegans. Genetic and reconstitution studies revealed that the potent body fat phenotype of gpa-3 null mutants is controlled from a pair of neurons called ADL(L/R). We show that cAMP functions as the second messenger in the ADL neurons, and regulates body fat stores via the neurotransmitter acetylcholine, from downstream neurons. We find that the pheromone ascr#3, which is detected by the ADL neurons, regulates body fat stores in a GPA-3-dependent manner. We define here a third sensory modality, pheromone sensing, as a major regulator of body fat metabolism. The pheromone ascr#3 is an indicator of population density, thus we hypothesize that pheromone sensing provides a salient 'denominator' to evaluate the amount of food available within a population and to accordingly adjust metabolic rate and body fat levels.

  15. Delayed innocent bystander cell death following hypoxia in Caenorhabditis elegans.

    Science.gov (United States)

    Sun, C-L; Kim, E; Crowder, C M

    2014-04-01

    After hypoxia, cells may die immediately or have a protracted course, living or dying depending on an incompletely understood set of cell autonomous and nonautonomous factors. In stroke, for example, some neurons are thought to die from direct hypoxic injury by cell autonomous primary mechanisms, whereas other so called innocent bystander neurons die from factors released from the primarily injured cells. A major limitation in identifying these factors is the inability of current in vivo models to selectively target a set of cells for hypoxic injury so that the primarily injured cells and the innocent bystanders are clearly delineated. In order to develop such a model, we generated transgenic Caenorhabditis elegans strains where 2-3% of somatic cells were made selectively sensitive to hypoxia. This was accomplished by cell type-specific wild-type rescue in either pharyngeal myocytes or GABAergic neurons of a hypoxia resistance-producing translation factor mutation. Surprisingly, hypoxic targeting of these relatively small subsets of non-essential cells produced widespread innocent bystander cell injury, behavioral dysfunction and eventual organismal death. The hypoxic injury phenotypes of the myocyte or neuron sensitized strains were virtually identical. Using this model, we show that the C. elegans insulin receptor/FOXO transcription factor pathway improves survival when activated only after hypoxic injury and blocks innocent bystander death.

  16. A Caenorhabditis elegans Mass Spectrometric Resource for Neuropeptidomics

    Science.gov (United States)

    Van Bael, Sven; Zels, Sven; Boonen, Kurt; Beets, Isabel; Schoofs, Liliane; Temmerman, Liesbet

    2018-01-01

    Neuropeptides are important signaling molecules used by nervous systems to mediate and fine-tune neuronal communication. They can function as neurotransmitters or neuromodulators in neural circuits, or they can be released as neurohormones to target distant cells and tissues. Neuropeptides are typically cleaved from larger precursor proteins by the action of proteases and can be the subject of post-translational modifications. The short, mature neuropeptide sequences often entail the only evolutionarily reasonably conserved regions in these precursor proteins. Therefore, it is particularly challenging to predict all putative bioactive peptides through in silico mining of neuropeptide precursor sequences. Peptidomics is an approach that allows de novo characterization of peptides extracted from body fluids, cells, tissues, organs, or whole-body preparations. Mass spectrometry, often combined with on-line liquid chromatography, is a hallmark technique used in peptidomics research. Here, we used an acidified methanol extraction procedure and a quadrupole-Orbitrap LC-MS/MS pipeline to analyze the neuropeptidome of Caenorhabditis elegans. We identified an unprecedented number of 203 mature neuropeptides from C. elegans whole-body extracts, including 35 peptides from known, hypothetical, as well as from completely novel neuropeptide precursor proteins that have not been predicted in silico. This set of biochemically verified peptide sequences provides the most elaborate C. elegans reference neurpeptidome so far. To exploit this resource to the fullest, we make our in-house database of known and predicted neuropeptides available to the community as a valuable resource. We are providing these collective data to help the community progress, amongst others, by supporting future differential and/or functional studies.

  17. A Caenorhabditis elegans Mass Spectrometric Resource for Neuropeptidomics

    Science.gov (United States)

    Van Bael, Sven; Zels, Sven; Boonen, Kurt; Beets, Isabel; Schoofs, Liliane; Temmerman, Liesbet

    2018-05-01

    Neuropeptides are important signaling molecules used by nervous systems to mediate and fine-tune neuronal communication. They can function as neurotransmitters or neuromodulators in neural circuits, or they can be released as neurohormones to target distant cells and tissues. Neuropeptides are typically cleaved from larger precursor proteins by the action of proteases and can be the subject of post-translational modifications. The short, mature neuropeptide sequences often entail the only evolutionarily reasonably conserved regions in these precursor proteins. Therefore, it is particularly challenging to predict all putative bioactive peptides through in silico mining of neuropeptide precursor sequences. Peptidomics is an approach that allows de novo characterization of peptides extracted from body fluids, cells, tissues, organs, or whole-body preparations. Mass spectrometry, often combined with on-line liquid chromatography, is a hallmark technique used in peptidomics research. Here, we used an acidified methanol extraction procedure and a quadrupole-Orbitrap LC-MS/MS pipeline to analyze the neuropeptidome of Caenorhabditis elegans. We identified an unprecedented number of 203 mature neuropeptides from C. elegans whole-body extracts, including 35 peptides from known, hypothetical, as well as from completely novel neuropeptide precursor proteins that have not been predicted in silico. This set of biochemically verified peptide sequences provides the most elaborate C. elegans reference neurpeptidome so far. To exploit this resource to the fullest, we make our in-house database of known and predicted neuropeptides available to the community as a valuable resource. We are providing these collective data to help the community progress, amongst others, by supporting future differential and/or functional studies. [Figure not available: see fulltext.

  18. On Modelling an Immune System

    OpenAIRE

    Monroy, Raúl; Saab, Rosa; Godínez, Fernando

    2004-01-01

    Immune systems of live forms have been an abundant source of inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to challenging problems of modern computing. However, research in artificial immune systems has overlooked establishing a coherent model of known immune system behaviour. This paper aims reports on an preliminary computer model of an immune system, where each immune system component...

  19. Expression of ceramide glucosyltransferases, which are essential for glycosphingolipid synthesis, is only required in a small subset of C. elegans cells

    DEFF Research Database (Denmark)

    Marza, Esther; Simonsen, Karina T; Færgeman, Nils J

    2009-01-01

    mutants with essentially no GSLs. The C. elegans genome encodes three ceramide glucosyltransferase (CGT) genes, which encode enzymes required for GSL biosynthesis. Animals lacking CGT do not synthesize GSLs, arrest growth at the first larval stage, and display defects in a subset of cells...... suggest that GSLs are dispensable in most C. elegans cells, including those of the nervous system.......Glycosphingolipids (GSLs) are glycosylated derivatives of ceramide in the lipid bilayer. Their ubiquitous distribution and complexity suggest that they have important functions, but what these are in vivo is still poorly understood. Here, we characterize the phenotype of Caenorhabditis elegans...

  20. Peroxisome protein transportation affects metabolism of branched-chain fatty acids that critically impact growth and development of C. elegans.

    Directory of Open Access Journals (Sweden)

    Rencheng Wang

    Full Text Available The impact of specific lipid molecules, including fatty acid variants, on cellular and developmental regulation is an important research subject that remains under studied. Monomethyl branched-chain fatty acids (mmBCFAs are commonly present in multiple organisms including mammals, however our understanding of mmBCFA functions is very limited. C. elegans has been the premier model system to study the functions of mmBCFAs and their derived lipids, as mmBCFAs have been shown to play essential roles in post-embryonic development in this organism. To understand more about the metabolism of mmBCFAs in C. elegans, we performed a genetic screen for suppressors of the L1 developmental arrest phenotype caused by mmBCFA depletion. Extensive characterization of one suppressor mutation identified prx-5, which encodes an ortholog of the human receptor for the type-1 peroxisomal targeting signal protein. Our study showed that inactivating prx-5 function compromised the peroxisome protein import, resulting in an increased level of branched-chain fatty acid C17ISO in animals lacking normal mmBCFA synthesis, thereby restoring wild-type growth and development. This work reveals a novel connection between peroxisomal functions and mmBCFA metabolism.

  1. Calycophyllum spruceanum (Benth., the Amazonian “Tree of Youth” Prolongs Longevity and Enhances Stress Resistance in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Herbenya Peixoto

    2018-02-01

    Full Text Available The tree popularly known in Brazil as mulateiro or pau-mulato (Calycophyllum spruceanum (Benth. K. Schum. is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers. For this investigation, we used the model system Caenorhabditis elegans to evaluate in vivo antioxidant and anti-aging activity of a water extract from C. spruceanum. To chemically characterize the extract, HPLC MS (High Performance Liquid Chromatography Mass Spectrometry/MS analyses were performed. Five secondary metabolites were identified in the extract, namely gardenoside, 5-hydroxymorin, cyanidin, taxifolin, and 5-hydroxy-6-methoxycoumarin-7-glucoside. C. spruceanum extract was able to enhance stress resistance and to extend lifespan along with attenuation of aging-associated markers in C. elegans. The demonstrated bioactivities apparently depend on the DAF-16/FOXO pathway. The data might support the popular claims of mulateiro as the “tree of youth”, however more studies are needed to clarify its putative benefits to human health.

  2. Pembangunan Model Restaurant Management System

    OpenAIRE

    Fredy Jingga; Natalia Limantara

    2014-01-01

    Model design for Restaurant Management System aims to help in restaurant business process, where Restaurant Management System (RMS) help the waitress and chef could interact each other without paper limitation.  This Restaurant Management System Model develop using Agile Methodology and developed based on PHP Programming Langguage. The database management system is using MySQL. This web-based application model will enable the waitress and the chef to interact in realtime, from the time they a...

  3. Modelling of wastewater systems

    DEFF Research Database (Denmark)

    Bechmann, Henrik

    to analyze and quantify the effect of the Aeration Tank Settling (ATS) operating mode, which is used during rain events. Furthermore, the model is used to propose a control algorithm for the phase lengths during ATS operation. The models are mainly formulated as state space model in continuous time......In this thesis, models of pollution fluxes in the inlet to 2 Danish wastewater treatment plants (WWTPs) as well as of suspended solids (SS) concentrations in the aeration tanks of an alternating WWTP and in the effluent from the aeration tanks are developed. The latter model is furthermore used...... at modelling the fluxes in terms of the multiple correlation coefficient R2. The model of the SS concentrations in the aeration tanks of an alternating WWTP as well as in the effluent from the aeration tanks is a mass balance model based on measurements of SS in one aeration tank and in the common outlet...

  4. Selenium species-dependent toxicity, bioavailability and metabolic transformations in Caenorhabditis elegans.

    Science.gov (United States)

    Rohn, Isabelle; Marschall, Talke Anu; Kroepfl, Nina; Jensen, Kenneth Bendix; Aschner, Michael; Tuck, Simon; Kuehnelt, Doris; Schwerdtle, Tanja; Bornhorst, Julia

    2018-05-17

    The essential micronutrient selenium (Se) is required for various systemic functions, but its beneficial range is narrow and overexposure may result in adverse health effects. Additionally, the chemical form of the ingested selenium contributes crucially to its health effects. While small Se species play a major role in Se metabolism, their toxicological effects, bioavailability and metabolic transformations following elevated uptake are poorly understood. Utilizing the tractable invertebrate Caenorhabditis elegans allowed for an alternative approach to study species-specific characteristics of organic and inorganic Se forms in vivo, revealing remarkable species-dependent differences in the toxicity and bioavailability of selenite, selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys). An inverse relationship was found between toxicity and bioavailability of the Se species, with the organic species displaying a higher bioavailability than the inorganic form, yet being less toxic. Quantitative Se speciation analysis with HPLC/mass spectrometry revealed a partial metabolism of SeMet and MeSeCys. In SeMet exposed worms, identified metabolites were Se-adenosylselenomethionine (AdoSeMet) and Se-adenosylselenohomocysteine (AdoSeHcy), while worms exposed to MeSeCys produced Se-methylselenoglutathione (MeSeGSH) and γ-glutamyl-MeSeCys (γ-Glu-MeSeCys). Moreover, the possible role of the sole selenoprotein in the nematode, thioredoxin reductase-1 (TrxR-1), was studied comparing wildtype and trxr-1 deletion mutants. Although a lower basal Se level was detected in trxr-1 mutants, Se toxicity and bioavailability following acute exposure was indistinguishable from wildtype worms. Altogether, the current study demonstrates the suitability of C. elegans as a model for Se species dependent toxicity and metabolism, while further research is needed to elucidate TrxR-1 function in the nematode.

  5. Cellular stress induces a protective sleep-like state in C. elegans.

    Science.gov (United States)

    Hill, Andrew J; Mansfield, Richard; Lopez, Jessie M N G; Raizen, David M; Van Buskirk, Cheryl

    2014-10-20

    Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis. These models are supported by the identification of synaptic and metabolic processes that are perturbed during prolonged wakefulness. It remains to be seen whether perturbations of cellular homeostasis in turn drive sleep. Here we show that under conditions of cellular stress, including noxious heat, cold, hypertonicity, and tissue damage, the nematode Caenorhabditis elegans engages a behavioral quiescence program. The stress-induced quiescent state displays properties of sleep and is dependent on the ALA neuron, which mediates the conserved soporific effect of epidermal growth factor (EGF) ligand overexpression. We characterize heat-induced quiescence in detail and show that it is indeed dependent on components of EGF signaling, providing physiological relevance to the behavioral effects of EGF family ligands. We find that after noxious heat exposure, quiescence-defective animals show elevated expression of cellular stress reporter genes and are impaired for survival, demonstrating the benefit of stress-induced behavioral quiescence. These data provide evidence that cellular stress can induce a protective sleep-like state in C. elegans and suggest that a deeply conserved function of sleep is to mitigate disruptions of cellular homeostasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Modeling and estimating system availability

    International Nuclear Information System (INIS)

    Gaver, D.P.; Chu, B.B.

    1976-11-01

    Mathematical models to infer the availability of various types of more or less complicated systems are described. The analyses presented are probabilistic in nature and consist of three parts: a presentation of various analytic models for availability; a means of deriving approximate probability limits on system availability; and a means of statistical inference of system availability from sparse data, using a jackknife procedure. Various low-order redundant systems are used as examples, but extension to more complex systems is not difficult

  7. Toxicity-based toxicokinetic/toxicodynamic assessment of bioaccumulation and nanotoxicity of zerovalent iron nanoparticles in Caenorhabditis elegans.

    Science.gov (United States)

    Yang, Ying-Fei; Lin, Yi-Jun; Liao, Chung-Min

    2017-01-01

    Elucidating the relationships between the toxicity-based-toxicokinetic (TBTK)/toxicodynamic (TD) properties of engineered nanomaterials and their nanotoxicity is crucial for human health-risk analysis. Zerovalent iron (Fe 0 ) nanoparticles (NPs) are one of the most prominent NPs applied in remediating contaminated soils and groundwater. However, there are concerns that Fe 0 NP application contributes to long-term environmental and human health impacts. The nematode Caenorhabditis elegans is a surrogate in vivo model that has been successfully applied to assess the potential nanotoxicity of these nanomaterials. Here we present a TBTK/TD approach to appraise bioaccumulation and nanotoxicity of Fe 0 NPs in C. elegans . Built on a present C. elegans bioassay with estimated TBTK/TD parameters, we found that average bioconcentration factors in C. elegans exposed to waterborne and food-borne Fe 0 NPs were ~50 and ~5×10 -3 , respectively, whereas 10% inhibition concentrations for fertility, locomotion, and development, were 1.26 (95% CI 0.19-5.2), 3.84 (0.38-42), and 6.78 (2.58-21) μg·g -1 , respectively, implicating that fertility is the most sensitive endpoint in C. elegans . Our results also showed that biomagnification effects were not observed in waterborne or food-borne Fe 0 NP-exposed worms. We suggest that the TBTK/TD assessment for predicting NP-induced toxicity at different concentrations and conditions in C. elegans could enable rapid selection of nanomaterials that are more likely to be nontoxic in larger animals. We conclude that the use of the TBTK/TD scheme manipulating C. elegans could be used for rapid evaluation of in vivo toxicity of NPs or for drug screening in the field of nanomedicine.

  8. Computational Methods for Tracking, Quantitative Assessment, and Visualization of C. elegans Locomotory Behavior.

    Directory of Open Access Journals (Sweden)

    Kyle Moy

    Full Text Available The nematode Caenorhabditis elegans provides a unique opportunity to interrogate the neural basis of behavior at single neuron resolution. In C. elegans, neural circuits that control behaviors can be formulated based on its complete neural connection map, and easily assessed by applying advanced genetic tools that allow for modulation in the activity of specific neurons. Importantly, C. elegans exhibits several elaborate behaviors that can be empirically quantified and analyzed, thus providing a means to assess the contribution of specific neural circuits to behavioral output. Particularly, locomotory behavior can be recorded and analyzed with computational and mathematical tools. Here, we describe a robust single worm-tracking system, which is based on the open-source Python programming language, and an analysis system, which implements path-related algorithms. Our tracking system was designed to accommodate worms that explore a large area with frequent turns and reversals at high speeds. As a proof of principle, we used our tracker to record the movements of wild-type animals that were freshly removed from abundant bacterial food, and determined how wild-type animals change locomotory behavior over a long period of time. Consistent with previous findings, we observed that wild-type animals show a transition from area-restricted local search to global search over time. Intriguingly, we found that wild-type animals initially exhibit short, random movements interrupted by infrequent long trajectories. This movement pattern often coincides with local/global search behavior, and visually resembles Lévy flight search, a search behavior conserved across species. Our mathematical analysis showed that while most of the animals exhibited Brownian walks, approximately 20% of the animals exhibited Lévy flights, indicating that C. elegans can use Lévy flights for efficient food search. In summary, our tracker and analysis software will help analyze the

  9. Humidity sensation requires both mechanosensory and thermosensory pathways in Caenorhabditis elegans.

    Science.gov (United States)

    Russell, Joshua; Vidal-Gadea, Andrés G; Makay, Alex; Lanam, Carolyn; Pierce-Shimomura, Jonathan T

    2014-06-03

    All terrestrial animals must find a proper level of moisture to ensure their health and survival. The cellular-molecular basis for sensing humidity is unknown in most animals, however. We used the model nematode Caenorhabditis elegans to uncover a mechanism for sensing humidity. We found that whereas C. elegans showed no obvious preference for humidity levels under standard culture conditions, worms displayed a strong preference after pairing starvation with different humidity levels, orienting to gradients as shallow as 0.03% relative humidity per millimeter. Cell-specific ablation and rescue experiments demonstrate that orientation to humidity in C. elegans requires the obligatory combination of distinct mechanosensitive and thermosensitive pathways. The mechanosensitive pathway requires a conserved DEG/ENaC/ASIC mechanoreceptor complex in the FLP neuron pair. Because humidity levels influence the hydration of the worm's cuticle, our results suggest that FLP may convey humidity information by reporting the degree that subcuticular dendritic sensory branches of FLP neurons are stretched by hydration. The thermosensitive pathway requires cGMP-gated channels in the AFD neuron pair. Because humidity levels affect evaporative cooling, AFD may convey humidity information by reporting thermal flux. Thus, humidity sensation arises as a metamodality in C. elegans that requires the integration of parallel mechanosensory and thermosensory pathways. This hygrosensation strategy, first proposed by Thunberg more than 100 y ago, may be conserved because the underlying pathways have cellular and molecular equivalents across a wide range of species, including insects and humans.

  10. Behavioral and metabolic effects of the atypical antipsychotic ziprasidone on the nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Priscila Gubert

    Full Text Available Atypical antipsychotics are associated with metabolic syndrome, primarily associated with weight gain. The effects of Ziprasidone, an atypical antipsychotic, on metabolic syndrome has yet to be evaluated. Here in, we evaluated lipid accumulation and behavioral changes in a new experimental model, the nematode Caenorhabditis elegans (C. elegans. Behavioral parameters in the worms were evaluated 24 h after Ziprasidone treatment. Subsequently, lipid accumulation was examined using Nile red, LipidTox green and BODIPY labeling. Ziprasidone at 40 µM for 24 h effectively decreased the fluorescence labeling of all markers in intestinal cells of C. elegans compared to control (0.16% dimethyl sulfoxide. Ziprasidone did not alter behaviors related to energetic balance, such as pharynx pumping, defecation cycles and movement. There was, however, a reduction in egg-production, egg-laying and body-length in nematodes exposed to Ziprasidone without any changes in the progression of larval stages. The serotoninergic pathway did not appear to modulate Ziprasidone's effects on Nile red fluorescence. Additionally, Ziprasidone did not alter lipid accumulation in daf-16 or crh-1 deletion mutants (orthologous of the transcription factors DAF-16 and CREB, respectively. These results suggest that Ziprasidone alters reproductive behavior, morphology and lipid reserves in the intestinal cells of C. elegans. Our results highlight that the DAF-16 and CREB transcription factors are essential for Ziprasidone-induced fat store reduction.

  11. Gengnianchun Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1 Signalling Pathway

    Directory of Open Access Journals (Sweden)

    Fanhui Meng

    2018-01-01

    Full Text Available Gengnianchun (GNC, a traditional Chinese medicine (TCM, is believed to have beneficial effects on ageing-related diseases, such as antioxidant properties and effects against Aβ-induced toxicity. We previously found that GNC extended the lifespan of Caenorhabditis elegans. However, the mechanism underlying this effect was unclear. In this study, we further explored the mechanisms of GNC using a C. elegans model. GNC significantly increased the lifespan of C. elegans and enhanced oxidative and thermal stress resistance. Moreover, chemotaxis increased after GNC treatment. RNA-seq analysis showed that GNC regulated genes associated with longevity. We also conducted lifespan assays with a series of worm mutants. The results showed that GNC significantly extended the lifespan of several mutant strains, including eat-2 (ad465, rsks-1 (ok1255, and glp-1 (e2144, suggesting that the prolongevity effect of GNC is independent of the function of these genes. However, GNC failed to extend the lifespan of daf-2 (e1370, age-1 (hx546, and daf-16 (mu86 mutant strains. Our findings suggest that GNC extends the lifespan of C. elegans via the insulin/IGF-1 signalling pathway and may be a potential antiageing agent.

  12. Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans.

    Science.gov (United States)

    Vita-More, Natasha; Barranco, Daniel

    2015-10-01

    Can memory be retained after cryopreservation? Our research has attempted to answer this long-standing question by using the nematode worm Caenorhabditis elegans, a well-known model organism for biological research that has generated revolutionary findings but has not been tested for memory retention after cryopreservation. Our study's goal was to test C. elegans' memory recall after vitrification and reviving. Using a method of sensory imprinting in the young C. elegans, we establish that learning acquired through olfactory cues shapes the animal's behavior and the learning is retained at the adult stage after vitrification. Our research method included olfactory imprinting with the chemical benzaldehyde (C6H5CHO) for phase-sense olfactory imprinting at the L1 stage, the fast-cooling SafeSpeed method for vitrification at the L2 stage, reviving, and a chemotaxis assay for testing memory retention of learning at the adult stage. Our results in testing memory retention after cryopreservation show that the mechanisms that regulate the odorant imprinting (a form of long-term memory) in C. elegans have not been modified by the process of vitrification or by slow freezing.

  13. Modeling soft interface dominated systems

    NARCIS (Netherlands)

    Lamorgese, A.; Mauri, R.; Sagis, L.M.C.

    2017-01-01

    The two main continuum frameworks used for modeling the dynamics of soft multiphase systems are the Gibbs dividing surface model, and the diffuse interface model. In the former the interface is modeled as a two dimensional surface, and excess properties such as a surface density, or surface energy

  14. Piceatannol extends the lifespan of Caenorhabditis elegans via DAF-16.

    Science.gov (United States)

    Shen, Peiyi; Yue, Yiren; Sun, Quancai; Kasireddy, Nandita; Kim, Kee-Hong; Park, Yeonhwa

    2017-05-06

    Piceatannol is a natural stilbene with many beneficial effects, such as antioxidative, anti-inflammatory, antiatherogenic activities; however, its role on aging is not known. In this study, we used Caenorhabditis elegans as an animal model to study the effect of piceatannol on its lifespan and investigated the underlying mechanisms. The results showed that 50 and 100 µM piceatannol significantly extended the lifespan of C. elegans without altering the growth rate, worm size and progeny production. Piceatannol delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress. This study further indicated that lifespan extension and enhanced stress resistance induced by piceatannol requires DAF-16. Since DAF-16 is conserved from nematodes to mammals, our study may have important implications in utilizing piceatannol to promote healthy aging and combat age-related disease in humans. © 2016 BioFactors, 43(3):379-387, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  15. Adverse Effects of Hydroalcoholic Extracts and the Major Components in the Stems of Impatiens balsamina L. on Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Hong-Fang Jiang

    2017-01-01

    Full Text Available Impatiens balsamina L. (Balsaminaceae, an annual herb found throughout China, has been extensively used in traditional Chinese medicine (TCM. However, our knowledge regarding the adverse effects of I. balsamina in vivo is very limited. In this present study, the nematode Caenorhabditis elegans model was employed to fully assess the adverse effects of hydroalcoholic (EtOH 55% extracts of I. balsamina stems (HAEIBS in vivo. After exposure to 10 mg/mL HAEIBS, the major organism-level endpoints of C. elegans of percent survival, frequency of head thrash and body bends, and reproduction had decreased by 24%, 30%, and 25%, respectively. The lifespan of C. elegans was also greatly reduced after HAEIBS exposure compared to the controls. The active compounds in HAEIBS were separated using high speed countercurrent chromatograph (HSCCC and characterized by high performance liquid chromatography (HPLC and nuclear magnetic resonance (NMR. Two compounds, lawsone and 2-methoxy-1,4-naphthoquinone (MNQ, and their adverse effects were then more thoroughly detailed in this study. It was found that lawsone is the major toxin in HAEIBS with a higher toxicity than MNQ in terms of negative impact on C. elegans mortality, locomotion, reproduction, and lifespan. Our data also suggests that the C. elegans model may be useful for assessing the possible toxicity of other Chinese medicines, plant extracts, and/or compounds.

  16. Tracking C. elegans and its neuromuscular activity using NemaFlex

    Science.gov (United States)

    van Bussel, Frank; Rahman, Mizanur; Hewitt, Jennifer; Blawzdziewicz, Jerzy; Driscoll, Monica; Szewczyk, Nathaniel; Vanapalli, Siva

    Recently, a novel platform has been developed for studying the behavior and physical characteristics of the nematode C. elegans. This is NemaFlex, developed by the Vanapalli group at Texas Tech University to analyze movement and muscular strength of crawling C. elegans. NemaFlex is a microfluidic device consisting of an array of deformable PDMS pillars, with which the C. elegans interacts in the course of moving through the system. Deflection measurements then allow us to calculate the force exerted by the worm via Euler-Bernoulli beam theory. For the procedure to be fully automated a fairly sophisticated software analysis has to be developed in tandem with the physical device. In particular, the usefulness of the force calculations is highly dependent on the accuracy and volume of the deflection measurements, which would be prohibitively time-consuming if carried out by hand/eye. In order to correlate the force results with muscle activations the C. elegans itself has to be tracked simultaneously, and pillar deflections precisely associated with mechanical-contact on the worm's body. Here we will outline the data processing and analysis routines that have been implemented in order to automate the calculation of these forces and muscular activations.

  17. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. The overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  18. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Boozer, D.D.; Hulme, B.L.; Daniel, S.L.; Varnado, G.B.; Bennett, H.A.; Chapman, L.D.; Engi, D.

    1976-09-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. In this paper, the overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  19. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. In this paper, the overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  20. DAF-16: FOXO in the Context of C. elegans.

    Science.gov (United States)

    Tissenbaum, Heidi A

    2018-01-01

    In Caenorhabditis elegans, there is a single FOXO transcription factor homolog, encoded by the gene, daf-16. As a central regulator for multiple signaling pathways, DAF-16 integrates these signals which results in modulation of several biological processes including longevity, development, fat storage, stress resistance, innate immunity, and reproduction. Using C. elegans allows for studies of FOXO in the context of the whole animal. Therefore, manipulating levels or the activity of daf-16 results in phenotypic changes. Genetic and molecular analysis revealed that similar to other systems, DAF-16 is the downstream target of the conserved insulin/IGF-1 signaling (IIS) pathway; a PI 3-kinase/AKT signaling cascade that ultimately controls the regulation of DAF-16 nuclear localization. In this chapter, I will focus on understanding how a single gene daf-16 can incorporate signals from multiple upstream pathways and in turn modulate different phenotypes as well as the study of FOXO in the context of a whole organism. © 2018 Elsevier Inc. All rights reserved.

  1. ECONOMIC MODELING STOCKS CONTROL SYSTEM: SIMULATION MODEL

    OpenAIRE

    Климак, М.С.; Войтко, С.В.

    2016-01-01

    Considered theoretical and applied aspects of the development of simulation models to predictthe optimal development and production systems that create tangible products andservices. It isproved that theprocessof inventory control needs of economicandmathematical modeling in viewof thecomplexity of theoretical studies. A simulation model of stocks control that allows make managementdecisions with production logistics

  2. Comparative assessment of fluorescent proteins for in vivo imaging in an animal model system.

    Science.gov (United States)

    Heppert, Jennifer K; Dickinson, Daniel J; Pani, Ariel M; Higgins, Christopher D; Steward, Annette; Ahringer, Julie; Kuhn, Jeffrey R; Goldstein, Bob

    2016-11-07

    Fluorescent protein tags are fundamental tools used to visualize gene products and analyze their dynamics in vivo. Recent advances in genome editing have expedited the precise insertion of fluorescent protein tags into the genomes of diverse organisms. These advances expand the potential of in vivo imaging experiments and facilitate experimentation with new, bright, photostable fluorescent proteins. Most quantitative comparisons of the brightness and photostability of different fluorescent proteins have been made in vitro, removed from biological variables that govern their performance in cells or organisms. To address the gap, we quantitatively assessed fluorescent protein properties in vivo in an animal model system. We generated transgenic Caenorhabditis elegans strains expressing green, yellow, or red fluorescent proteins in embryos and imaged embryos expressing different fluorescent proteins under the same conditions for direct comparison. We found that mNeonGreen was not as bright in vivo as predicted based on in vitro data but is a better tag than GFP for specific kinds of experiments, and we report on optimal red fluorescent proteins. These results identify ideal fluorescent proteins for imaging in vivo in C. elegans embryos and suggest good candidate fluorescent proteins to test in other animal model systems for in vivo imaging experiments. © 2016 Heppert et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. An atlas of Caenorhabditis elegans chemoreceptor expression.

    Directory of Open Access Journals (Sweden)

    Berta Vidal

    2018-01-01

    Full Text Available One goal of modern day neuroscience is the establishment of molecular maps that assign unique features to individual neuron types. Such maps provide important starting points for neuron classification, for functional analysis, and for developmental studies aimed at defining the molecular mechanisms of neuron identity acquisition and neuron identity diversification. In this resource paper, we describe a nervous system-wide map of the potential expression sites of 244 members of the largest gene family in the C. elegans genome, rhodopsin-like (class A G-protein-coupled receptor (GPCR chemoreceptors, using classic gfp reporter gene technology. We cover representatives of all sequence families of chemoreceptor GPCRs, some of which were previously entirely uncharacterized. Most reporters are expressed in a very restricted number of cells, often just in single cells. We assign GPCR reporter expression to all but two of the 37 sensory neuron classes of the sex-shared, core nervous system. Some sensory neurons express a very small number of receptors, while others, particularly nociceptive neurons, coexpress several dozen GPCR reporter genes. GPCR reporters are also expressed in a wide range of inter- and motorneurons, as well as non-neuronal cells, suggesting that GPCRs may constitute receptors not just for environmental signals, but also for internal cues. We observe only one notable, frequent association of coexpression patterns, namely in one nociceptive amphid (ASH and two nociceptive phasmid sensory neurons (PHA, PHB. We identified GPCRs with sexually dimorphic expression and several GPCR reporters that are expressed in a left/right asymmetric manner. We identified a substantial degree of GPCR expression plasticity; particularly in the context of the environmentally-induced dauer diapause stage when one third of all tested GPCRs alter the cellular specificity of their expression within and outside the nervous system. Intriguingly, in a number of

  4. Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*

    Science.gov (United States)

    Andrusiak, Matthew G.; Jin, Yishi

    2016-01-01

    Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundworm Caenorhabditis elegans was developed as a system to study genes required for development and nervous system function. The powerful genetics of C. elegans in combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components in C. elegans. PMID:26907690

  5. EGL-13/SoxD Specifies Distinct O2 and CO2 Sensory Neuron Fates in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Gramstrup Petersen, Jakob; Rojo Romanos, Teresa; Juozaityte, Vaida

    2013-01-01

    that EGL-13 is sufficient to induce O2- and CO2-sensing cell fates in some cellular contexts. Thus, the same core regulatory factor, egl-13, is required and sufficient to specify the distinct fates of O2- and CO2-sensing neurons in C. elegans. These findings extend our understanding of mechanisms......Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O2) and carbon dioxide (CO2). In Caenorhabditis elegans, the O2/CO2 sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral...

  6. Shigella flexneri infection in Caenorhabditis elegans: cytopathological examination and identification of host responses.

    Directory of Open Access Journals (Sweden)

    Divya T George

    Full Text Available The Gram-negative bacterium Shigella flexneri is the causative agent of shigellosis, a diarrhoeal disease also known as bacillary dysentery. S. flexneri infects the colonic and rectal epithelia of its primate host and induces a cascade of inflammatory responses that culminates in the destruction of the host intestinal lining. Molecular characterization of host-pathogen interactions in this infection has been challenging due to the host specificity of S. flexneri strains, as it strictly infects humans and non-human primates. Recent studies have shown that S. flexneri infects the soil dwelling nematode Caenorhabditis elegans, however, the interactions between S. flexneri and C. elegans at the cellular level and the cause of nematode death are unknown. Here we attempt to gain insight into the complex host-pathogen interactions between S. flexneri and C. elegans. Using transmission electron microscopy, we show that live S. flexneri cells accumulate in the nematode intestinal lumen, produce outer membrane vesicles and invade nematode intestinal cells. Using two-dimensional differential in-gel electrophoresis we identified host proteins that are differentially expressed in response to S. flexneri infection. Four of the identified genes, aco-1, cct-2, daf-19 and hsp-60, were knocked down using RNAi and ACO-1, CCT-2 and DAF-19, which were identified as up-regulated in response to S. flexneri infection, were found to be involved in the infection process. aco-1 RNAi worms were more resistant to S. flexneri infection, suggesting S. flexneri-mediated disruption of host iron homeostasis. cct-2 and daf-19 RNAi worms were more susceptible to infection, suggesting that these genes are induced as a protective mechanism by C. elegans. These observations further our understanding of the processes involved in S. flexneri infection of C. elegans, which is immensely beneficial to the routine use of this new in vivo model to study S. flexneri pathogenesis.

  7. Transgenic C. elegans dauer larvae expressing hookworm phospho null DAF-16/FoxO exit dauer.

    Directory of Open Access Journals (Sweden)

    Verena Gelmedin

    Full Text Available Parasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3 in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from L3 arrest during infection. Lacking reverse genetic techniques for use in hookworms, we used C. elegans complementation assays to investigate the function of Ancylostoma caninum DAF-16 during entrance and exit from L3 developmental arrest. We performed dauer switching assays and observed the restoration of the dauer phenotype when Ac-DAF-16 was expressed in temperature-sensitive dauer defective C. elegans daf-2(e1370;daf-16(mu86 mutants. AKT phosphorylation site mutants of Ac-DAF-16 were also able to restore the dauer phenotype, but surprisingly allowed dauer exit when temperatures were lowered. We used fluorescence microscopy to localize DAF-16 during dauer and exit from dauer in C. elegans DAF-16 mutant worms expressing Ac-DAF-16, and found that Ac-DAF-16 exited the nucleus during dauer exit. Surprisingly, Ac-DAF-16 with mutated AKT phosphorylation sites also exited the nucleus during dauer exit. Our results suggest that another mechanism may be involved in the regulation DAF-16 nuclear localization during recovery from developmental arrest.

  8. Bioinformatics analysis identify novel OB fold protein coding genes in C. elegans.

    Directory of Open Access Journals (Sweden)

    Daryanaz Dargahi

    Full Text Available BACKGROUND: The C. elegans genome has been extensively annotated by the WormBase consortium that uses state of the art bioinformatics pipelines, functional genomics and manual curation approaches. As a result, the identification of novel genes in silico in this model organism is becoming more challenging requiring new approaches. The Oligonucleotide-oligosaccharide binding (OB fold is a highly divergent protein family, in which protein sequences, in spite of having the same fold, share very little sequence identity (5-25%. Therefore, evidence from sequence-based annotation may not be sufficient to identify all the members of this family. In C. elegans, the number of OB-fold proteins reported is remarkably low (n=46 compared to other evolutionary-related eukaryotes, such as yeast S. cerevisiae (n=344 or fruit fly D. melanogaster (n=84. Gene loss during evolution or differences in the level of annotation for this protein family, may explain these discrepancies. METHODOLOGY/PRINCIPAL FINDINGS: This study examines the possibility that novel OB-fold coding genes exist in the worm. We developed a bioinformatics approach that uses the most sensitive sequence-sequence, sequence-profile and profile-profile similarity search methods followed by 3D-structure prediction as a filtering step to eliminate false positive candidate sequences. We have predicted 18 coding genes containing the OB-fold that have remarkably partially been characterized in C. elegans. CONCLUSIONS/SIGNIFICANCE: This study raises the possibility that the annotation of highly divergent protein fold families can be improved in C. elegans. Similar strategies could be implemented for large scale analysis by the WormBase consortium when novel versions of the genome sequence of C. elegans, or other evolutionary related species are being released. This approach is of general interest to the scientific community since it can be used to annotate any genome.

  9. The G protein-coupled receptor FSHR-1 is required for the Caenorhabditis elegans innate immune response.

    Science.gov (United States)

    Powell, Jennifer R; Kim, Dennis H; Ausubel, Frederick M

    2009-02-24

    Innate immunity is an ancient defense system used by both vertebrates and invertebrates. Previously characterized innate immune responses in plants and animals are triggered by detection of pathogens using specific receptors, which typically use a leucine-rich repeat (LRR) domain to bind molecular patterns associated with infection. The nematode Caenorhabditis elegans uses defense pathways conserved with vertebrates; however, the mechanism by which C. elegans detects pathogens is unknown. We screened all LRR-containing transmembrane receptors in C. elegans and identified the G protein-coupled receptor FSHR-1 as an important component of the C. elegans immune response to Gram-negative and Gram-positive bacterial pathogens. FSHR-1 acts in the C. elegans intestine, the primary site of exposure to ingested pathogens. FSHR-1 signals in parallel to the known p38 MAPK pathway but converges to regulate the transcriptional induction of an overlapping but nonidentical set of antimicrobial effectors. FSHR-1 may act generally to boost the nematode immune response, or it may function as a pathogen receptor.

  10. ASN reputation system model

    Science.gov (United States)

    Hutchinson, Steve; Erbacher, Robert F.

    2015-05-01

    Network security monitoring is currently challenged by its reliance on human analysts and the inability for tools to generate indications and warnings for previously unknown attacks. We propose a reputation system based on IP address set membership within the Autonomous System Number (ASN) system. Essentially, a metric generated based on the historic behavior, or misbehavior, of nodes within a given ASN can be used to predict future behavior and provide a mechanism to locate network activity requiring inspection. This will provide reinforcement of notifications and warnings and lead to inspection for ASNs known to be problematic even if initial inspection leads to interpretation of the event as innocuous. We developed proof of concept capabilities to generate the IP address to ASN set membership and analyze the impact of the results. These results clearly show that while some ASNs are one-offs with individual or small numbers of misbehaving IP addresses, there are definitive ASNs with a history of long term and wide spread misbehaving IP addresses. These ASNs with long histories are what we are especially interested in and will provide an additional correlation metric for the human analyst and lead to new tools to aid remediation of these IP address blocks.

  11. Visible light reduces C. elegans longevity.

    Science.gov (United States)

    De Magalhaes Filho, C Daniel; Henriquez, Brian; Seah, Nicole E; Evans, Ronald M; Lapierre, Louis R; Dillin, Andrew

    2018-03-02

    The transparent nematode Caenorhabditis elegans can sense UV and blue-violet light to alter behavior. Because high-dose UV and blue-violet light are not a common feature outside of the laboratory setting, we asked what role, if any, could low-intensity visible light play in C. elegans physiology and longevity. Here, we show that C. elegans lifespan is inversely correlated to the time worms were exposed to visible light. While circadian control, lite-1 and tax-2 do not contribute to the lifespan reduction, we demonstrate that visible light creates photooxidative stress along with a general unfolded-protein response that decreases the lifespan. Finally, we find that long-lived mutants are more resistant to light stress, as well as wild-type worms supplemented pharmacologically with antioxidants. This study reveals that transparent nematodes are sensitive to visible light radiation and highlights the need to standardize methods for controlling the unrecognized biased effect of light during lifespan studies in laboratory conditions.

  12. Acute carbon dioxide avoidance in Caenorhabditis elegans.

    Science.gov (United States)

    Hallem, Elissa A; Sternberg, Paul W

    2008-06-10

    Carbon dioxide is produced as a by-product of cellular respiration by all aerobic organisms and thus serves for many animals as an important indicator of food, mates, and predators. However, whether free-living terrestrial nematodes such as Caenorhabditis elegans respond to CO2 was unclear. We have demonstrated that adult C. elegans display an acute avoidance response upon exposure to CO2 that is characterized by the cessation of forward movement and the rapid initiation of backward movement. This response is mediated by a cGMP signaling pathway that includes the cGMP-gated heteromeric channel TAX-2/TAX-4. CO2 avoidance is modulated by multiple signaling molecules, including the neuropeptide Y receptor NPR-1 and the calcineurin subunits TAX-6 and CNB-1. Nutritional status also modulates CO2 responsiveness via the insulin and TGFbeta signaling pathways. CO2 response is mediated by a neural circuit that includes the BAG neurons, a pair of sensory neurons of previously unknown function. TAX-2/TAX-4 function in the BAG neurons to mediate acute CO2 avoidance. Our results demonstrate that C. elegans senses and responds to CO2 using multiple signaling pathways and a neural network that includes the BAG neurons and that this response is modulated by the physiological state of the worm.

  13. Anti-Aging and Antioxidant Potential of Paullinia cupana var. sorbilis: Findings in Caenorhabditis elegans Indicate a New Utilization for Roasted Seeds of Guarana.

    Science.gov (United States)

    Peixoto, Herbenya; Roxo, Mariana; Röhrig, Teresa; Richling, Elke; Wang, Xiaojuan; Wink, Michael

    2017-08-15

    Background: Roasted seeds of Amazonian guarana ( Paullinia cupana var. sorbilis; Sapindaceae) are popular in South America due to their stimulant activity on the central nervous system (CNS). Rich in purine alkaloids, markedly caffeine, the seeds are extensively used in the Brazilian beverage industry for the preparation of soft drinks and as additives in energy drinks. Methods: To investigate the putative anti-aging and antioxidant activity of guarana, we used the model organism Caenorhabditis elegans . Chemical analyses were performed using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS/MS). Results: When tested in the model system Caenorhabditis elegans , the water extract from roasted guarana seeds enhanced resistance against oxidative stress, extended lifespan and attenuated aging markers such as muscle function decline and polyQ40 aggregation. Conclusions: In the current study, we demonstrate that guarana extracts can work as a powerful antioxidant in vivo; moreover, guarana extracts exhibit anti-aging properties. Our results suggest that the biological activities of guarana go beyond the extensively reported CNS stimulation.

  14. Stochastic Modelling of Energy Systems

    DEFF Research Database (Denmark)

    Andersen, Klaus Kaae

    2001-01-01

    is that the model structure has to be adequate for practical applications, such as system simulation, fault detection and diagnosis, and design of control strategies. This also reflects on the methods used for identification of the component models. The main result from this research is the identification......In this thesis dynamic models of typical components in Danish heating systems are considered. Emphasis is made on describing and evaluating mathematical methods for identification of such models, and on presentation of component models for practical applications. The thesis consists of seven...... research papers (case studies) together with a summary report. Each case study takes it's starting point in typical heating system components and both, the applied mathematical modelling methods and the application aspects, are considered. The summary report gives an introduction to the scope...

  15. Role for β-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions

    Science.gov (United States)

    Irazoqui, Javier E.; Ng, Aylwin; Xavier, Ramnik J.; Ausubel, Frederick M.

    2008-01-01

    We used the model nematode Caenorhabditis elegans infected with the human pathogen Staphylococcus aureus to identify components of epithelial immunity. Transcriptional profiling and reverse genetic analysis revealed that mutation of the C. elegans β-catenin homolog bar-1 or the downstream homeobox gene egl-5 results in a defective response and hypersensitivity to S. aureus infection. Epistasis analysis showed that bar-1 and egl-5 function in parallel to previously described C. elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-κB-dependent TLR2 signaling in epithelial cells. These data suggest that β-catenin and homeobox genes play an important and conserved role in innate immune defense. PMID:18981407

  16. Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions.

    Science.gov (United States)

    Irazoqui, Javier E; Ng, Aylwin; Xavier, Ramnik J; Ausubel, Frederick M

    2008-11-11

    We used the model nematode Caenorhabditis elegans infected with the human pathogen Staphylococcus aureus to identify components of epithelial immunity. Transcriptional profiling and reverse genetic analysis revealed that mutation of the C. elegans beta-catenin homolog bar-1 or the downstream homeobox gene egl-5 results in a defective response and hypersensitivity to S. aureus infection. Epistasis analysis showed that bar-1 and egl-5 function in parallel to previously described C. elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-kappaB-dependent TLR2 signaling in epithelial cells. These data suggest that beta-catenin and homeobox genes play an important and conserved role in innate immune defense.

  17. Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway

    DEFF Research Database (Denmark)

    Fang, Evandro Fei; Waltz, Tyler B; Kassahun, Henok

    2017-01-01

    in human aging. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits age-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in C. elegans, an animal model of aging which shares many major longevity pathways with mammals. Tomatidine improves...... many C. elegans behaviors related to healthspan and muscle health, including increased pharyngeal pumping, swimming movement, and reduced percentage of severely damaged muscle cells. Microarray, imaging, and behavioral analyses reveal that tomatidine maintains mitochondrial homeostasis by modulating...... occurs in C. elegans, primary rat neurons, and human cells. Our data suggest that tomatidine may delay some physiological aspects of aging, and points to new approaches for pharmacological interventions for diseases of aging....

  18. HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1

    DEFF Research Database (Denmark)

    Shamalnasab, Mehrnaz; Dhaoui, Manel; Thondamal, Manjunatha

    2017-01-01

    In yeast, the broadly conserved acyl-CoA-binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode C. elegans as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically...... inactivated each of the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to different types of stress. Through genetic and gene...... of the proteome. Our work extends to C. elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan of maa-1-deficient worms, and sheds light on the anti-aging function of HIF-1. Given that both ACBP and HIF-1 are highly conserved, our results suggest the possible involvement of these proteins...

  19. Stress Erythropoiesis Model Systems.

    Science.gov (United States)

    Bennett, Laura F; Liao, Chang; Paulson, Robert F

    2018-01-01

    Bone marrow steady-state erythropoiesis maintains erythroid homeostasis throughout life. This process constantly generates new erythrocytes to replace the senescent erythrocytes that are removed by macrophages in the spleen. In contrast, anemic or hypoxic stress induces a physiological response designed to increase oxygen delivery to the tissues. Stress erythropoiesis is a key component of this response. It is best understood in mice where it is extramedullary occurring in the adult spleen and liver and in the fetal liver during development. Stress erythropoiesis utilizes progenitor cells and signals that are distinct from bone marrow steady-state erythropoiesis. Because of that observation many genes may play a role in stress erythropoiesis despite having no effect on steady-state erythropoiesis. In this chapter, we will discuss in vivo and in vitro techniques to study stress erythropoiesis in mice and how the in vitro culture system can be extended to study human stress erythropoiesis.

  20. Distribution system modeling and analysis

    CERN Document Server

    Kersting, William H

    2001-01-01

    For decades, distribution engineers did not have the sophisticated tools developed for analyzing transmission systems-often they had only their instincts. Things have changed, and we now have computer programs that allow engineers to simulate, analyze, and optimize distribution systems. Powerful as these programs are, however, without a real understanding of the operating characteristics of a distribution system, engineers using the programs can easily make serious errors in their designs and operating procedures. Distribution System Modeling and Analysis helps prevent those errors. It gives readers a basic understanding of the modeling and operating characteristics of the major components of a distribution system. One by one, the author develops and analyzes each component as a stand-alone element, then puts them all together to analyze a distribution system comprising the various shunt and series devices for power-flow and short-circuit studies. He includes the derivation of all models and includes many num...

  1. Data management system performance modeling

    Science.gov (United States)

    Kiser, Larry M.

    1993-01-01

    This paper discusses analytical techniques that have been used to gain a better understanding of the Space Station Freedom's (SSF's) Data Management System (DMS). The DMS is a complex, distributed, real-time computer system that has been redesigned numerous times. The implications of these redesigns have not been fully analyzed. This paper discusses the advantages and disadvantages for static analytical techniques such as Rate Monotonic Analysis (RMA) and also provides a rationale for dynamic modeling. Factors such as system architecture, processor utilization, bus architecture, queuing, etc. are well suited for analysis with a dynamic model. The significance of performance measures for a real-time system are discussed.

  2. Model systems in photosynthesis research

    International Nuclear Information System (INIS)

    Katz, J.J.; Hindman, J.C.

    1981-01-01

    After a general discussion of model studies in photosynthesis research, three recently developed model systems are described. The current status of covalently linked chlorophyll pairs as models for P700 and P865 is first briefly reviewed. Mg-tris(pyrochlorophyllide)1,1,1-tris(hydroxymethyl) ethane triester in its folded configuration is then discussed as a rudimentary antenna-photoreaction center model. Finally, self-assembled chlorophyll systems that contain a mixture of monomeric, oligomeric and special pair chlorophyll are shown to have fluorescence emission characteristics that resemble thoe of intact Tribonema aequale at room temperature in that both show fluorescence emission at 675 and 695 nm. In the self-assembled systems the wavelength of the emitted fluorescence depends on the wavelength of excitation, arguing that energy transfer between different chlorophyll species in these systems may be more complex than previously suspected

  3. Mobility Models for Systems Evaluation

    Science.gov (United States)

    Musolesi, Mirco; Mascolo, Cecilia

    Mobility models are used to simulate and evaluate the performance of mobile wireless systems and the algorithms and protocols at the basis of them. The definition of realistic mobility models is one of the most critical and, at the same time, difficult aspects of the simulation of applications and systems designed for mobile environments. There are essentially two possible types of mobility patterns that can be used to evaluate mobile network protocols and algorithms by means of simulations: traces and synthetic models [130]. Traces are obtained by means of measurements of deployed systems and usually consist of logs of connectivity or location information, whereas synthetic models are mathematical models, such as sets of equations, which try to capture the movement of the devices.

  4. WormScan: a technique for high-throughput phenotypic analysis of Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Mark D Mathew

    Full Text Available BACKGROUND: There are four main phenotypes that are assessed in whole organism studies of Caenorhabditis elegans; mortality, movement, fecundity and size. Procedures have been developed that focus on the digital analysis of some, but not all of these phenotypes and may be limited by expense and limited throughput. We have developed WormScan, an automated image acquisition system that allows quantitative analysis of each of these four phenotypes on standard NGM plates seeded with E. coli. This system is very easy to implement and has the capacity to be used in high-throughput analysis. METHODOLOGY/PRINCIPAL FINDINGS: Our system employs a readily available consumer grade flatbed scanner. The method uses light stimulus from the scanner rather than physical stimulus to induce movement. With two sequential scans it is possible to quantify the induced phototactic response. To demonstrate the utility of the method, we measured the phenotypic response of C. elegans to phosphine gas exposure. We found that stimulation of movement by the light of the scanner was equivalent to physical stimulation for the determination of mortality. WormScan also provided a quantitative assessment of health for the survivors. Habituation from light stimulation of continuous scans was similar to habituation caused by physical stimulus. CONCLUSIONS/SIGNIFICANCE: There are existing systems for the automated phenotypic data collection of C. elegans. The specific advantages of our method over existing systems are high-throughput assessment of a greater range of phenotypic endpoints including determination of mortality and quantification of the mobility of survivors. Our system is also inexpensive and very easy to implement. Even though we have focused on demonstrating the usefulness of WormScan in toxicology, it can be used in a wide range of additional C. elegans studies including lifespan determination, development, pathology and behavior. Moreover, we have even adapted the

  5. Stochastic Models of Polymer Systems

    Science.gov (United States)

    2016-01-01

    Distribution Unlimited Final Report: Stochastic Models of Polymer Systems The views, opinions and/or findings contained in this report are those of the...ADDRESS. Princeton University PO Box 0036 87 Prospect Avenue - 2nd floor Princeton, NJ 08544 -2020 14-Mar-2014 ABSTRACT Number of Papers published in...peer-reviewed journals: Number of Papers published in non peer-reviewed journals: Final Report: Stochastic Models of Polymer Systems Report Title

  6. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    Science.gov (United States)

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M.; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions. PMID:25699030

  7. Potential Nematode Alarm Pheromone Induces Acute Avoidance in Caenorhabditis elegans.

    Science.gov (United States)

    Zhou, Ying; Loeza-Cabrera, Mario; Liu, Zheng; Aleman-Meza, Boanerges; Nguyen, Julie K; Jung, Sang-Kyu; Choi, Yuna; Shou, Qingyao; Butcher, Rebecca A; Zhong, Weiwei

    2017-07-01

    It is crucial for animal survival to detect dangers such as predators. A good indicator of dangers is injury of conspecifics. Here we show that fluids released from injured conspecifics invoke acute avoidance in both free-living and parasitic nematodes. Caenorhabditis elegans avoids extracts from closely related nematode species but not fruit fly larvae. The worm extracts have no impact on animal lifespan, suggesting that the worm extract may function as an alarm instead of inflicting physical harm. Avoidance of the worm extract requires the function of a cGMP signaling pathway that includes the cGMP-gated channel TAX-2/TAX-4 in the amphid sensory neurons ASI and ASK. Genetic evidence indicates that the avoidance behavior is modulated by the neurotransmitters GABA and serotonin, two common targets of anxiolytic drugs. Together, these data support a model that nematodes use a nematode-specific alarm pheromone to detect conspecific injury. Copyright © 2017 by the Genetics Society of America.

  8. Radiation-induced gene expression in the nematode caenorhabditis elegans

    International Nuclear Information System (INIS)

    Nelson, G.A.; Jones, T.A.; Chesnut, A.; Smith, A.L.

    2002-01-01

    We used the nematode C. elegans to characterize the genotoxic and cytotoxic effects of ionizing radiation in a simple animal model emphasizing the unique effects of charged particle radiation. Here we demonstrate by reverse transcription polymerase chain reaction (RT-PCR) differential display and whole genome microarray hybridization experiments that gamma rays, accelerated protons and iron ions at the same physical dose lead to unique transcription profiles. 599 of 17871 genes analyzed (3.4%) showed differential expression 3 hrs after exposure to 3 Gy of radiation. 193 were up-regulated, 406 were down-regulated and 90% were affected only by a single species of radiation. A novel statistical clustering technique identified the regulatory relationships between the radiation-modulated genes and showed that genes affected by each radiation species were associated with unique regulatory clusters. This suggests that independent homeostatic mechanisms are activated in response to radiation exposure as a function of track structure or ionization density. (author)

  9. Dissecting the C. elegans response during infection using quantitative proteomics

    DEFF Research Database (Denmark)

    Simonsen, Karina Trankjær; Møller-Jensen, Jakob; Kristensen, Anders Riis

    2008-01-01

    The adherent invasive E. coli isolated from patients with Crohn’s disease in humans is pathogenic for C. elegans. We show here that when C. elegans feeds on the pathogenic E. coli, the life span is shortened significantly compared to the normal laboratory food, the OP50 E. coli. In this study...... the infection process is followed using GFP-expressing bacteria and persistence assays. A quantitative proteomic approach was used to follow the C. elegans host response during the infection process. C. elegans were metabolic labeled with the stable isotope 15N and samples from three different time points......, many of which also have been found in studies using other pathogens. So far, large-scale investigations of the C. elegans immune response have been performed using micro-arrays. This study is the first to make use of quantitative proteomics to directly follow the protein dynamics during the infection...

  10. National Energy Outlook Modelling System

    Energy Technology Data Exchange (ETDEWEB)

    Volkers, C.M. [ECN Policy Studies, Petten (Netherlands)

    2013-12-15

    For over 20 years, the Energy research Centre of the Netherlands (ECN) has been developing the National Energy Outlook Modelling System (NEOMS) for Energy projections and policy evaluations. NEOMS enables 12 energy models of ECN to exchange data and produce consistent and detailed results.

  11. Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio.

    Science.gov (United States)

    Vaccaro, Alexandra; Patten, Shunmoogum A; Ciura, Sorana; Maios, Claudia; Therrien, Martine; Drapeau, Pierre; Kabashi, Edor; Parker, J Alex

    2012-01-01

    The DNA/RNA-binding proteins TDP-43 and FUS are found in protein aggregates in a growing number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and related dementia, but little is known about the neurotoxic mechanisms. We have generated Caenorhabditis elegans and zebrafish animal models expressing mutant human TDP-43 (A315T or G348C) or FUS (S57Δ or R521H) that reflect certain aspects of ALS including motor neuron degeneration, axonal deficits, and progressive paralysis. To explore the potential of our humanized transgenic C. elegans and zebrafish in identifying chemical suppressors of mutant TDP-43 and FUS neuronal toxicity, we tested three compounds with potential neuroprotective properties: lithium chloride, methylene blue and riluzole. We identified methylene blue as a potent suppressor of TDP-43 and FUS toxicity in both our models. Our results indicate that methylene blue can rescue toxic phenotypes associated with mutant TDP-43 and FUS including neuronal dysfunction and oxidative stress.

  12. Flow-Based Network Analysis of the Caenorhabditis elegans Connectome.

    Science.gov (United States)

    Bacik, Karol A; Schaub, Michael T; Beguerisse-Díaz, Mariano; Billeh, Yazan N; Barahona, Mauricio

    2016-08-01

    We exploit flow propagation on the directed neuronal network of the nematode C. elegans to reveal dynamically relevant features of its connectome. We find flow-based groupings of neurons at different levels of granularity, which we relate to functional and anatomical constituents of its nervous system. A systematic in silico evaluation of the full set of single and double neuron ablations is used to identify deletions that induce the most severe disruptions of the multi-resolution flow structure. Such ablations are linked to functionally relevant neurons, and suggest potential candidates for further in vivo investigation. In addition, we use the directional patterns of incoming and outgoing network flows at all scales to identify flow profiles for the neurons in the connectome, without pre-imposing a priori categories. The four flow roles identified are linked to signal propagation motivated by biological input-response scenarios.

  13. Aerodynamic and Mechanical System Modelling

    DEFF Research Database (Denmark)

    Jørgensen, Martin Felix

    This thesis deals with mechanical multibody-systems applied to the drivetrain of a 500 kW wind turbine. Particular focus has been on gearbox modelling of wind turbines. The main part of the present project involved programming multibody systems to investigate the connection between forces, moments...

  14. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...

  15. A multi-endpoint, high-throughput study of nanomaterial toxicity in Caenorhabditis elegans

    Science.gov (United States)

    Jung, Sang-Kyu; Qu, Xiaolei; Aleman-Meza, Boanerges; Wang, Tianxiao; Riepe, Celeste; Liu, Zheng; Li, Qilin; Zhong, Weiwei

    2015-01-01

    The booming nanotech industry has raised public concerns about the environmental health and safety impact of engineered nanomaterials (ENMs). High-throughput assays are needed to obtain toxicity data for the rapidly increasing number of ENMs. Here we present a suite of high-throughput methods to study nanotoxicity in intact animals using Caenorhabditis elegans as a model. At the population level, our system measures food consumption of thousands of animals to evaluate population fitness. At the organism level, our automated system analyzes hundreds of individual animals for body length, locomotion speed, and lifespan. To demonstrate the utility of our system, we applied this technology to test the toxicity of 20 nanomaterials under four concentrations. Only fullerene nanoparticles (nC60), fullerol, TiO2, and CeO2 showed little or no toxicity. Various degrees of toxicity were detected from different forms of carbon nanotubes, graphene, carbon black, Ag, and fumed SiO2 nanoparticles. Aminofullerene and UV irradiated nC60 also showed small but significant toxicity. We further investigated the effects of nanomaterial size, shape, surface chemistry, and exposure conditions on toxicity. Our data are publicly available at the open-access nanotoxicity database www.QuantWorm.org/nano. PMID:25611253

  16. Developmental wiring of specific neurons is regulated by RET-1/Nogo-A in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Torpe, Nanna; Nørgaard, Steffen; Høye, Anette M.

    2017-01-01

    Nogo-A is a membrane-bound protein that functions to inhibit neuronal migration, adhesion, and neurite outgrowth during development. In the mature nervous system, Nogo-A stabilizes neuronal wiring to inhibit neuronal plasticity and regeneration after injury. Here, we show that RET-1, the sole Nog...... present a previously unidentified function for RET-1 in the nervous system of C. elegans.......-A homolog in Caenorhabditis elegans, is required to control developmental wiring of a specific subset of neurons. In ret-1 deletion mutant animals, specific ventral nerve cord axons are misguided where they fail to respect the ventral midline boundary. We found that ret-1 is expressed in multiple neurons...

  17. Mechanisms of Plasticity in a Caenorhabditis elegans Mechanosensory Circuit

    Directory of Open Access Journals (Sweden)

    Tahereh eBozorgmehr

    2013-08-01

    Full Text Available Despite having a small nervous system (302 neurons and relatively short lifespan (14-21 days, the nematode Caenorhabditis elegans has a substantial ability to change its behavior in response to experience. The behaviour discussed here is the tap withdrawal response, whereby the worm crawls backwards a brief distance in response to a non-localized stimulus to the side of the Petri plate within which it lives. The neural circuit that underlies this behaviour is primarily made up of 5 sensory neurons and four pairs of interneurons. In this review we describe two classes of mechanosensory plasticity: adult learning and memory and experience dependent changes during development. As worms develop through young adult and adult stages there is a shift towards deeper habituation of response probability that is likely the result of changes in sensitivity to stimulus intensity. Adult worms show short- intermediate- and long-term habituation as well as context dependent habituation. Short-term habituation requires glutamate signalling and auto-phosphorylation of voltage-dependent potassium channels and is modulated by dopamine signalling in the mechanosensory neurons. Long-term memory for habituation is mediated by down-regulation of expression of an AMPA-type glutamate receptor subunit. Intermediate memory involves an increase in release of an inhibitory neuropeptide. Depriving larval worms of mechanosensory stimulation early in development leads to fewer synaptic vesicles in the mechanosensory neurons and lower levels of an AMPA-type glutamate receptor subunit in the interneurons. Overall, the mechanosensory system of C. elegans shows a great deal of experience dependent plasticity both during development and as an adult. The simplest form of learning, habituation, is not so simple and is mediated and/or modulated by a number of different processes, some of which we are beginning to understand.

  18. Motorneurons dedicated to either forward or backward locomotion in the nematode C. elegans

    OpenAIRE

    Haspel, Gal; O'Donovan, Michael J.; Hart, Anne C.

    2010-01-01

    Multifunctional motorneurons and muscles, which are active during forward and backward locomotion and driven by common central pattern generators, are ubiquitous in animal models. However, studies in the nematode Caenorhabditis elegans suggest that some locomotor motorneurons are necessary only for forward locomotion (dorsal B-motorneurons, DB) while others (dorsal A-motorneurons, DA) are necessary only for backward locomotion. We tested this hypothesis directly by recording the activity of t...

  19. Modeling Multi-Level Systems

    CERN Document Server

    Iordache, Octavian

    2011-01-01

    This book is devoted to modeling of multi-level complex systems, a challenging domain for engineers, researchers and entrepreneurs, confronted with the transition from learning and adaptability to evolvability and autonomy for technologies, devices and problem solving methods. Chapter 1 introduces the multi-scale and multi-level systems and highlights their presence in different domains of science and technology. Methodologies as, random systems, non-Archimedean analysis, category theory and specific techniques as model categorification and integrative closure, are presented in chapter 2. Chapters 3 and 4 describe polystochastic models, PSM, and their developments. Categorical formulation of integrative closure offers the general PSM framework which serves as a flexible guideline for a large variety of multi-level modeling problems. Focusing on chemical engineering, pharmaceutical and environmental case studies, the chapters 5 to 8 analyze mixing, turbulent dispersion and entropy production for multi-scale sy...

  20. Pembangunan Model Restaurant Management System

    Directory of Open Access Journals (Sweden)

    Fredy Jingga

    2014-12-01

    Full Text Available Model design for Restaurant Management System aims to help in restaurant business process, where Restaurant Management System (RMS help the waitress and chef could interact each other without paper limitation.  This Restaurant Management System Model develop using Agile Methodology and developed based on PHP Programming Langguage. The database management system is using MySQL. This web-based application model will enable the waitress and the chef to interact in realtime, from the time they accept the customer order until the chef could know what to cook and checklist for the waitress wheter the order is fullfill or not, until the cahsier that will calculate the bill and the payment that they accep from the customer.

  1. EOL-1, the homolog of the mammalian Dom3Z, regulates olfactory learning in C. elegans

    OpenAIRE

    Zhang, J; Calarco, JA; Shen, Y; Zhang, Y

    2014-01-01

    Learning is an essential function of the nervous system. However, our understanding of molecular underpinnings of learning remains incomplete. Here, we characterize a conserved protein EOL-1 that regulates olfactory learning in Caenorhabditis elegans. A recessive allele of eol-1 (enhanced olfactory learning) learns better to adjust its olfactory preference for bacteria foods and eol-1 acts in the URX sensory neurons to regulate learning. The mammalian homolog of EOL-1, Dom3Z, which regulates ...

  2. Dauer pheromone and G-protein signaling modulate the coordination of intraflagellar transport kinesin motor proteins in C. elegans

    NARCIS (Netherlands)

    J.A. Burghoorn (Jan); M.P.J. Dekkers (Martijn); S. Rademakers (Suzanne); A.A.W. de Jong (Ton); R. Willemsen (Rob); P. Swoboda (Peter); J. McCafferty (Gert)

    2010-01-01

    textabstractCilia length and function are dynamically regulated by modulation of intraflagellar transport (IFT). The cilia of C. elegans amphid channel neurons provide an excellent model to study this process, since they use two different kinesins for anterograde transport: kinesin-II and OSM-3

  3. Models of complex attitude systems

    DEFF Research Database (Denmark)

    Sørensen, Bjarne Taulo

    search algorithms and structural equation models. The results suggest that evaluative judgments of the importance of production system attributes are generated in a schematic manner, driven by personal value orientations. The effect of personal value orientations was strong and largely unmediated...... that evaluative affect propagates through the system in such a way that the system becomes evaluatively consistent and operates as a schema for the generation of evaluative judgments. In the empirical part of the paper, the causal structure of an attitude system from which people derive their evaluations of pork......Existing research on public attitudes towards agricultural production systems is largely descriptive, abstracting from the processes through which members of the general public generate their evaluations of such systems. The present paper adopts a systems perspective on such evaluations...

  4. Automated Processing of Imaging Data through Multi-tiered Classification of Biological Structures Illustrated Using Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Mei Zhan

    2015-04-01

    Full Text Available Quantitative imaging has become a vital technique in biological discovery and clinical diagnostics; a plethora of tools have recently been developed to enable new and accelerated forms of biological investigation. Increasingly, the capacity for high-throughput experimentation provided by new imaging modalities, contrast techniques, microscopy tools, microfluidics and computer controlled systems shifts the experimental bottleneck from the level of physical manipulation and raw data collection to automated recognition and data processing. Yet, despite their broad importance, image analysis solutions to address these needs have been narrowly tailored. Here, we present a generalizable formulation for autonomous identification of specific biological structures that is applicable for many problems. The process flow architecture we present here utilizes standard image processing techniques and the multi-tiered application of classification models such as support vector machines (SVM. These low-level functions are readily available in a large array of image processing software packages and programming languages. Our framework is thus both easy to implement at the modular level and provides specific high-level architecture to guide the solution of more complicated image-processing problems. We demonstrate the utility of the classification routine by developing two specific classifiers as a toolset for automation and cell identification in the model organism Caenorhabditis elegans. To serve a common need for automated high-resolution imaging and behavior applications in the C. elegans research community, we contribute a ready-to-use classifier for the identification of the head of the animal under bright field imaging. Furthermore, we extend our framework to address the pervasive problem of cell-specific identification under fluorescent imaging, which is critical for biological investigation in multicellular organisms or tissues. Using these examples as a

  5. Automated Processing of Imaging Data through Multi-tiered Classification of Biological Structures Illustrated Using Caenorhabditis elegans.

    Science.gov (United States)

    Zhan, Mei; Crane, Matthew M; Entchev, Eugeni V; Caballero, Antonio; Fernandes de Abreu, Diana Andrea; Ch'ng, QueeLim; Lu, Hang

    2015-04-01

    Quantitative imaging has become a vital technique in biological discovery and clinical diagnostics; a plethora of tools have recently been developed to enable new and accelerated forms of biological investigation. Increasingly, the capacity for high-throughput experimentation provided by new imaging modalities, contrast techniques, microscopy tools, microfluidics and computer controlled systems shifts the experimental bottleneck from the level of physical manipulation and raw data collection to automated recognition and data processing. Yet, despite their broad importance, image analysis solutions to address these needs have been narrowly tailored. Here, we present a generalizable formulation for autonomous identification of specific biological structures that is applicable for many problems. The process flow architecture we present here utilizes standard image processing techniques and the multi-tiered application of classification models such as support vector machines (SVM). These low-level functions are readily available in a large array of image processing software packages and programming languages. Our framework is thus both easy to implement at the modular level and provides specific high-level architecture to guide the solution of more complicated image-processing problems. We demonstrate the utility of the classification routine by developing two specific classifiers as a toolset for automation and cell identification in the model organism Caenorhabditis elegans. To serve a common need for automated high-resolution imaging and behavior applications in the C. elegans research community, we contribute a ready-to-use classifier for the identification of the head of the animal under bright field imaging. Furthermore, we extend our framework to address the pervasive problem of cell-specific identification under fluorescent imaging, which is critical for biological investigation in multicellular organisms or tissues. Using these examples as a guide, we envision

  6. Making Sense of G Proteins: Genetic analysis of sensory G protein signaling in the nematode C. elegans

    NARCIS (Netherlands)

    H. Lans (Hannes)

    2005-01-01

    textabstractAmong the key molecules involved in sensory perception are G proteins, which act in every cell to activate a cascade of signaling molecules in response to certain environmental cues. In this thesis, several studies on the role of G proteins in the sensory system of C. elegans are

  7. Stirling Engine Dynamic System Modeling

    Science.gov (United States)

    Nakis, Christopher G.

    2004-01-01

    The Thermo-Mechanical systems branch at the Glenn Research Center focuses a large amount time on Stirling engines. These engines will be used on missions where solar power is inefficient, especially in deep space. I work with Tim Regan and Ed Lewandowski who are currently developing and validating a mathematical model for the Stirling engines. This model incorporates all aspects of the system including, mechanical, electrical and thermodynamic components. Modeling is done through Simplorer, a program capable of running simulations of the model. Once created and then proven to be accurate, a model is used for developing new ideas for engine design. My largest specific project involves varying key parameters in the model and quantifying the results. This can all be done relatively trouble-free with the help of Simplorer. Once the model is complete, Simplorer will do all the necessary calculations. The more complicated part of this project is determining which parameters to vary. Finding key parameters depends on the potential for a value to be independently altered in the design. For example, a change in one dimension may lead to a proportional change to the rest of the model, and no real progress is made. Also, the ability for a changed value to have a substantial impact on the outputs of the system is important. Results will be condensed into graphs and tables with the purpose of better communication and understanding of the data. With the changing of these parameters, a more optimal design can be created without having to purchase or build any models. Also, hours and hours of results can be simulated in minutes. In the long run, using mathematical models can save time and money. Along with this project, I have many other smaller assignments throughout the summer. My main goal is to assist in the processes of model development, validation and testing.

  8. Life cycle and population growth rate of Caenorhabditis elegans studied by a new method.

    Science.gov (United States)

    Muschiol, Daniel; Schroeder, Fabian; Traunspurger, Walter

    2009-05-16

    The free-living nematode Caenorhabditis elegans is the predominant model organism in biological research, being used by a huge number of laboratories worldwide. Many researchers have evaluated life-history traits of C. elegans in investigations covering quite different aspects such as ecotoxicology, inbreeding depression and heterosis, dietary restriction/supplement, mutations, and ageing. Such traits include juvenile growth rates, age at sexual maturity, adult body size, age-specific fecundity/mortality, total reproduction, mean and maximum lifespan, and intrinsic population growth rates. However, we found that in life-cycle experiments care is needed regarding protocol design. Here, we test a recently developed method that overcomes some problems associated with traditional cultivation techniques. In this fast and yet precise approach, single individuals are maintained within hanging drops of semi-fluid culture medium, allowing the simultaneous investigation of various life-history traits at any desired degree of accuracy. Here, the life cycles of wild-type C. elegans strains N2 (Bristol, UK) and MY6 (Münster, Germany) were compared at 20 degrees C with 5 x 10(9) Escherichia coli ml-1 as food source. High-resolution life tables and fecundity schedules of the two strains are presented. Though isolated 700 km and 60 years apart from each other, the two strains barely differed in life-cycle parameters. For strain N2 (n = 69), the intrinsic rate of natural increase (r m d(-1)), calculated according to the Lotka equation, was 1.375, the net reproductive rate (R 0) 291, the mean generation time (T) 90 h, and the minimum generation time (T min) 73.0 h. The corresponding values for strain MY6 (n = 72) were r m = 1.460, R0 = 289, T = 84 h, and T min = 67.3 h. Peak egg-laying rates in both strains exceeded 140 eggs d(-1). Juvenile and early adulthood mortality was negligible. Strain N2 lived, on average, for 16.7 d, while strain MY6 died 2 days earlier; however

  9. Life cycle and population growth rate of Caenorhabditis elegans studied by a new method

    Directory of Open Access Journals (Sweden)

    Schroeder Fabian

    2009-05-01

    Full Text Available Abstract Background The free-living nematode Caenorhabditis elegans is the predominant model organism in biological research, being used by a huge number of laboratories worldwide. Many researchers have evaluated life-history traits of C. elegans in investigations covering quite different aspects such as ecotoxicology, inbreeding depression and heterosis, dietary restriction/supplement, mutations, and ageing. Such traits include juvenile growth rates, age at sexual maturity, adult body size, age-specific fecundity/mortality, total reproduction, mean and maximum lifespan, and intrinsic population growth rates. However, we found that in life-cycle experiments care is needed regarding protocol design. Here, we test a recently developed method that overcomes some problems associated with traditional cultivation techniques. In this fast and yet precise approach, single individuals are maintained within hanging drops of semi-fluid culture medium, allowing the simultaneous investigation of various life-history traits at any desired degree of accuracy. Here, the life cycles of wild-type C. elegans strains N2 (Bristol, UK and MY6 (Münster, Germany were compared at 20°C with 5 × 109 Escherichia coli ml-1 as food source. Results High-resolution life tables and fecundity schedules of the two strains are presented. Though isolated 700 km and 60 years apart from each other, the two strains barely differed in life-cycle parameters. For strain N2 (n = 69, the intrinsic rate of natural increase (rmd-1, calculated according to the Lotka equation, was 1.375, the net reproductive rate (R0 291, the mean generation time (T 90 h, and the minimum generation time (Tmin 73.0 h. The corresponding values for strain MY6 (n = 72 were rm = 1.460, R0 = 289, T = 84 h, and Tmin = 67.3 h. Peak egg-laying rates in both strains exceeded 140 eggs d-1. Juvenile and early adulthood mortality was negligible. Strain N2 lived, on average, for 16.7 d, while strain MY6 died 2 days

  10. Malate and fumarate extend lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Clare B Edwards

    Full Text Available Malate, the tricarboxylic acid (TCA cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1, glyoxylate shunt (gei-7, succinate dehydrogenase flavoprotein (sdha-2, or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

  11. Photodynamic inactivation using curcuminoids and Photogem on caenorhabditis elegans

    Science.gov (United States)

    Albuquerque, Yulli R.; Pratavieira, Sebastião.; Bagnato, Vanderlei S.; Inada, Natalia M.; Souza, Larissa M.; Afonso, Ana; de Souza, Clovis W. O.; Oliveira, Kleber T.; Anibal, Fernanda F.

    2018-02-01

    Resistance to various anthelmintic drugs is reported in many animals and can become a severe problem for human and animal health. In this study, Photogem® and three curcuminoids compounds (curcumin, demethoxycurcumin, bisdemethoxycurcumin) were used as photosensitizers in the photodynamic inactivation (PDI) in the helminth model Caenorhabditis elegans to investigate the ability of this procedure to worm life cycle. Initially, the presence and location of the photosensitizers in the worm's body were verified by fluorescence confocal microscopy. Curcumin was deposited in the digestive tract and Photogem® along the body of the animal in the incubation time of 12 hours with the photosensitizer. Subsequently, a PDI procedure using a LED device was performed to illuminate the worms treated with the photosensitizers. The worms were observed by optical microscopy until 48 hours after the PDI to verify the changes in motility, the presence of eggs and larvae and the number of live worms. Curcuminoids tested separately and in combination and two light doses of 30 J/m2 no changes were observed in the life cycle of the worm at concentrations of 2 mM and 1 mM. However, in treatment with Photogem® and a light dose of 100 J/m2 a reduction in motility and reproduction of the worm with 0.2 mg/mL was observed after 6 hours of exposure, in addition to the death of most worms at concentrations of 6, 4, and 2 mg/mL. We suggest, therefore, that photodynamic inactivation with Photogem® may present an anthelmintic effect against C. elegans, but there is a need for studies on helminths with parasitic activity.

  12. Candida albicans infection of Caenorhabditis elegans induces antifungal immune defenses.

    Directory of Open Access Journals (Sweden)

    Read Pukkila-Worley

    2011-06-01

    Full Text Available Candida albicans yeast cells are found in the intestine of most humans, yet this opportunist can invade host tissues and cause life-threatening infections in susceptible individuals. To better understand the host factors that underlie susceptibility to candidiasis, we developed a new model to study antifungal innate immunity. We demonstrate that the yeast form of C. albicans establishes an intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected with C. albicans yeast showed that exposure to C. albicans stimulated a rapid host response involving 313 genes (124 upregulated and 189 downregulated, ~1.6% of the genome many of which encode antimicrobial, secreted or detoxification proteins. Interestingly, the host genes affected by C. albicans exposure overlapped only to a small extent with the distinct transcriptional responses to the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus, indicating that there is a high degree of immune specificity toward different bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa and S. aureus were strongly over-represented among the genes downregulated during C. albicans infection, suggesting that in response to fungal pathogens, nematodes selectively repress the transcription of antibacterial immune effectors. A similar phenomenon is well known in the plant immune response, but has not been described previously in metazoans. Finally, 56% of the genes induced by live C. albicans were also upregulated by heat-killed yeast. These data suggest that a large part of the transcriptional response to C. albicans is mediated through "pattern recognition," an ancient immune surveillance mechanism able to detect conserved microbial molecules (so-called pathogen-associated molecular patterns or PAMPs. This study provides new information on the evolution and regulation of the innate

  13. System Convergence in Transport Modelling

    DEFF Research Database (Denmark)

    Rich, Jeppe; Nielsen, Otto Anker; Cantarella, Guilio E.

    2010-01-01

    A fundamental premise of most applied transport models is the existence and uniqueness of an equilibrium solution that balances demand x(t) and supply t(x). The demand consists of the people that travel in the transport system and on the defined network, whereas the supply consists of the resulting...... level-of-service attributes (e.g., travel time and cost) offered to travellers. An important source of complexity is the congestion, which causes increasing demand to affect travel time in a non-linear way. Transport models most often involve separate models for traffic assignment and demand modelling...... iterating between a route-choice (demand) model and a time-flow (supply) model. It is generally recognised that a simple iteration scheme where the level-of-service level is fed directly to the route-choice and vice versa may exhibit an unstable pattern and lead to cyclic unstable solutions. It can be shown...

  14. Model Reduction of Hybrid Systems

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza

    gramians. Generalized gramians are the solutions to the observability and controllability Lyapunov inequalities. In the first framework the projection matrices are found based on the common generalized gramians. This framework preserves the stability of the original switched system for all switching...... is guaranteed to be preserved for arbitrary switching signal. To compute the common generalized gramians linear matrix inequalities (LMI’s) need to be solved. These LMI’s are not always feasible. In order to solve the problem of conservatism, the second framework is presented. In this method the projection......High-Technological solutions of today are characterized by complex dynamical models. A lot of these models have inherent hybrid/switching structure. Hybrid/switched systems are powerful models for distributed embedded systems design where discrete controls are applied to continuous processes...

  15. Numerical Modeling of Microelectrochemical Systems

    DEFF Research Database (Denmark)

    Adesokan, Bolaji James

    incorporates the finite size of ionic species in the transport equation. The model presents a more appropriate boundary conditions which describe the modified Butler-Volmer reaction kinetics and account for the surface capacitance of the thin electric double layer. We also have found analytical solution...... at the electrode in a microelectrochemical system. In our analysis, we account for the finite size properties of ions in the mass and the charge transport of ionic species in an electrochemical system. This term characterizes the saturation of the ionic species close to the electrode surface. We then analyse......The PhD dissertation is concerned with mathematical modeling and simulation of electrochemical systems. The first three chapters of the thesis consist of the introductory part, the model development chapter and the chapter on the summary of the main results. The remaining three chapters report...

  16. Undulatory swimming in viscoelastic fluids under geometric confinement: experiments with C. elegans

    Science.gov (United States)

    Gagnon, David; Shih, Jerry; Arratia, Paulo

    2017-11-01

    Many natural biological processes, such as bacteria moving through vesicles in the circulatory system and spermatozoa swimming through millimeter-scale fallopian tubes, require low Reynolds number swimmers to move between two fluid-solid interfaces. Furthermore, these biological systems typically involve non-Newtonian fluids (e.g. blood and mucus), which can be shear-thinning, viscoelastic, or both. Using the model biological organism C. elegans, we introduce two far-field no-slip boundary conditions in the beating plane by observing swimming through thin channels in viscosified Newtonian and viscoelastic fluids. Using image processing and particle tracking velocimetry techniques, we measure both the swimming kinematics and the resulting flow fields as a function of decreasing channel width. As this width approaches the characteristic transverse length scale of the nematode's swimming gate, we observe (i) swimming speed decreases with increasing De, (ii) this decrease in speed can be non-monotonic with decreasing channel width at a given De, and (iii) the change in nematode kinematics appears to be associated with a structural change in the flow field around the swimmer quantified using the flow type parameter.

  17. Biotransformation of furanocoumarins by Cunninghamella elegans

    Directory of Open Access Journals (Sweden)

    Ghada Ismail El-shahat Ali Attia

    2015-06-01

    Full Text Available Biotransformation of Furanocoumarins; psoralen (1, bergapten (2, xanthotoxin (3 and imperatorin (4 was explored by Cunninghamella elegans NRRL 1392, revealing the metabolism of psoralen (1 and bergapten (2 into bergaptol (5, while xanthotoxin (3 and imperatorin (4 were converted into xanthotoxol (6. On the other hand unexpected conversion of xanthotoxin (3 into 3,4 dihydroxanthotoxin (7 occurred. The structure of the isolated pure metabolites was established using physical and spectroscopic techniques including, melting points, IR, 1H NMR, 13C NMR and mass spectroscopy.

  18. Quantitative Assessment of Fat Levels in Caenorhabditis elegans Using Dark Field Microscopy

    Directory of Open Access Journals (Sweden)

    Anthony D. Fouad

    2017-06-01

    Full Text Available The roundworm Caenorhabditis elegans is widely used as a model for studying conserved pathways for fat storage, aging, and metabolism. The most broadly used methods for imaging fat in C. elegans require fixing and staining the animal. Here, we show that dark field images acquired through an ordinary light microscope can be used to estimate fat levels in worms. We define a metric based on the amount of light scattered per area, and show that this light scattering metric is strongly correlated with worm fat levels as measured by Oil Red O (ORO staining across a wide variety of genetic backgrounds and feeding conditions. Dark field imaging requires no exogenous agents or chemical fixation, making it compatible with live worm imaging. Using our method, we track fat storage with high temporal resolution in developing larvae, and show that fat storage in the intestine increases in at least one burst during development.

  19. Developmental Effects of the ToxCast™ Phase I and Phase II Chemicals in Caenorhabditis elegans and Corresponding Responses in Zebrafish, Rats, and Rabbits

    Science.gov (United States)

    Boyd, Windy A.; Smith, Marjolein V.; Co, Caroll A.; Pirone, Jason R.; Rice, Julie R.; Shockley, Keith R.; Freedman, Jonathan H.

    2015-01-01

    Background: Modern toxicology is shifting from an observational to a mechanistic science. As part of this shift, high-throughput toxicity assays are being developed using alternative, nonmammalian species to prioritize chemicals and develop prediction models of human toxicity. Methods: The nematode Caenorhabditis elegans (C. elegans) was used to screen the U.S. Environmental Protection Agency’s (EPA’s) ToxCast™ Phase I and Phase II libraries, which contain 292 and 676 chemicals, respectively, for chemicals leading to decreased larval development and growth. Chemical toxicity was evaluated using three parameters: a biologically defined effect size threshold, half-maximal activity concentration (AC50), and lowest effective concentration (LEC). Results: Across both the Phase I and Phase II libraries, 62% of the chemicals were classified as active ≤ 200 μM in the C. elegans assay. Chemical activities and potencies in C. elegans were compared with those from two zebrafish embryonic development toxicity studies and developmental toxicity data for rats and rabbits. Concordance of chemical activity was higher between C. elegans and one zebrafish assay across Phase I chemicals (79%) than with a second zebrafish assay (59%). Using C. elegans or zebrafish to predict rat or rabbit developmental toxicity resulted in balanced accuracies (the average value of the sensitivity and specificity for an assay) ranging from 45% to 53%, slightly lower than the concordance between rat and rabbit (58%). Conclusions: Here, we present an assay that quantitatively and reliably describes the effects of chemical toxicants on C. elegans growth and development. We found significant overlap in the activity of chemicals in the ToxCast™ libraries between C. elegans and zebrafish developmental screens. Incorporating C. elegans toxicological assays as part of a battery of in vitro and in vivo assays provides additional information for the development of models to predict a chemical

  20. Executive Information Systems' Multidimensional Models

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Executive Information Systems are design to improve the quality of strategic level of management in organization through a new type of technology and several techniques for extracting, transforming, processing, integrating and presenting data in such a way that the organizational knowledge filters can easily associate with this data and turn it into information for the organization. These technologies are known as Business Intelligence Tools. But in order to build analytic reports for Executive Information Systems (EIS in an organization we need to design a multidimensional model based on the business model from the organization. This paper presents some multidimensional models that can be used in EIS development and propose a new model that is suitable for strategic business requests.

  1. The computational worm: spatial orientation and its neuronal basis in C. elegans.

    Science.gov (United States)

    Lockery, Shawn R

    2011-10-01

    Spatial orientation behaviors in animals are fundamental for survival but poorly understood at the neuronal level. The nematode Caenorhabditis elegans orients to a wide range of stimuli and has a numerically small and well-described nervous system making it advantageous for investigating the mechanisms of spatial orientation. Recent work by the C. elegans research community has identified essential computational elements of the neural circuits underlying two orientation strategies that operate in five different sensory modalities. Analysis of these circuits reveals novel motifs including simple circuits for computing temporal derivatives of sensory input and for integrating sensory input with behavioral state to generate adaptive behavior. These motifs constitute hypotheses concerning the identity and functionality of circuits controlling spatial orientation in higher organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Optical silencing of C. elegans cells with light-driven proton pumps.

    Science.gov (United States)

    Okazaki, Ayako; Takahashi, Megumi; Toyoda, Naoya; Takagi, Shin

    2014-08-01

    Recent development of optogenetic techniques, which utilize light-driven ion channels or ion pumps for controlling the activity of excitable cells, has greatly facilitated the investigation of nervous systems in vivo. A new generation of optical silencers includes outward-directed proton pumps, such as Arch, which have several advantages over currently widely used halorhodopsin (NpHR). These advantages include the resistance to inactivation during prolonged illumination and the ability to generate a larger optical current from low intensity light. C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. In this article, we will outline the practical aspects of using of Arch and other proton pumps as optogenetic tools in C. elegans. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Turboelectric Distributed Propulsion System Modelling

    OpenAIRE

    Liu, Chengyuan

    2013-01-01

    The Blended-Wing-Body is a conceptual aircraft design with rear-mounted, over wing engines. Turboelectric distributed propulsion system with boundary layer ingestion has been considered for this aircraft. It uses electricity to transmit power from the core turbine to the fans, therefore dramatically increases bypass ratio to reduce fuel consumption and noise. This dissertation presents methods on designing the TeDP system, evaluating effects of boundary layer ingestion, modelling engine perfo...

  4. Cyanobacterial Xenobiotics as Evaluated by a Caenorhabditis elegans Neurotoxicity Screening Test

    Science.gov (United States)

    Ju, Jingjuan; Saul, Nadine; Kochan, Cindy; Putschew, Anke; Pu, Yuepu; Yin, Lihong; Steinberg, Christian E. W.

    2014-01-01

    In fresh waters cyanobacterial blooms can produce a variety of toxins, such as microcystin variants (MCs) and anatoxin-a (ANA). ANA is a well-known neurotoxin, whereas MCs are hepatotoxic and, to a lesser degree, also neurotoxic. Neurotoxicity applies especially to invertebrates lacking livers. Current standardized neurotoxicity screening methods use rats or mice. However, in order to minimize vertebrate animal experiments as well as experimental time and effort, many investigators have proposed the nematode Caenorhabditis elegans as an appropriate invertebrate model. Therefore, four known neurotoxic compounds (positive compounds: chlorpyrifos, abamectin, atropine, and acrylamide) were chosen to verify the expected impacts on autonomic (locomotion, feeding, defecation) and sensory (thermal, chemical, and mechanical sensory perception) functions in C. elegans. This study is another step towards successfully establishing C. elegans as an alternative neurotoxicity model. By using this protocol, anatoxin-a adversely affected locomotive behavior and pharyngeal pumping frequency and, most strongly, chemotactic and thermotactic behavior, whereas MC-LR impacted locomotion, pumping, and mechanical behavior, but not chemical sensory behavior. Environmental samples can also be screened in this simple and fast way for neurotoxic characteristics. The filtrate of a Microcystis aeruginosa culture, known for its hepatotoxicity, also displayed mild neurotoxicity (modulated short-term thermotaxis). These results show the suitability of this assay for environmental cyanotoxin-containing samples. PMID:24776722

  5. Turing mechanism for homeostatic control of synaptic density during C. elegans growth

    Science.gov (United States)

    Brooks, Heather A.; Bressloff, Paul C.

    2017-07-01

    We propose a mechanism for the homeostatic control of synapses along the ventral cord of Caenorhabditis elegans during development, based on a form of Turing pattern formation on a growing domain. C. elegans is an important animal model for understanding cellular mechanisms underlying learning and memory. Our mathematical model consists of two interacting chemical species, where one is passively diffusing and the other is actively trafficked by molecular motors, which switch between forward and backward moving states (bidirectional transport). This differs significantly from the standard mechanism for Turing pattern formation based on the interaction between fast and slow diffusing species. We derive evolution equations for the chemical concentrations on a slowly growing one-dimensional domain, and use numerical simulations to demonstrate the insertion of new concentration peaks as the length increases. Taking the passive component to be the protein kinase CaMKII and the active component to be the glutamate receptor GLR-1, we interpret the concentration peaks as sites of new synapses along the length of C. elegans, and thus show how the density of synaptic sites can be maintained.

  6. Video distribution system cost model

    Science.gov (United States)

    Gershkoff, I.; Haspert, J. K.; Morgenstern, B.

    1980-01-01

    A cost model that can be used to systematically identify the costs of procuring and operating satellite linked communications systems is described. The user defines a network configuration by specifying the location of each participating site, the interconnection requirements, and the transmission paths available for the uplink (studio to satellite), downlink (satellite to audience), and voice talkback (between audience and studio) segments of the network. The model uses this information to calculate the least expensive signal distribution path for each participating site. Cost estimates are broken downy by capital, installation, lease, operations and maintenance. The design of the model permits flexibility in specifying network and cost structure.

  7. Information Systems Outsourcing Relationship Model

    Directory of Open Access Journals (Sweden)

    Richard Flemming

    2007-09-01

    Full Text Available Increasing attention is being paid to what determines the success of an information systems outsourcing arrangement. The current research aims to provide an improved understanding of the factors influencing the outcome of an information systems outsourcing relationship and to provide a preliminary validation of an extended outsourcing relationship model by interviews with information systems outsourcing professionals in both the client and vendor of a major Australian outsourcing relationship. It also investigates whether the client and the vendor perceive the relationship differently and if so, how they perceive it differently and whether the two perspectives are interrelated.

  8. The C. elegans embryonic fate specification factor EGL-18 (GATA) is reutilized downstream of Wnt signaling to maintain a population of larval progenitor cells.

    Science.gov (United States)

    Gorrepati, Lakshmi; Eisenmann, David M

    2015-01-01

    In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further. Wnt signaling pathway is known to regulate the asymmetry of these divisions and maintain the progenitor cell fate in one daughter, but how activation of the Wnt pathway accomplished this was unknown. We describe here our recent work that identified the GATA transcription factor EGL-18 as a downstream target of Wnt signaling necessary for maintenance of a progenitor population of larval seam cells. EGL-18 was previously shown to act in the initial specification of the seam cells in the embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an embryonic fate specification factor to be reutilized later in life downstream of a different regulator (Wnt signaling) to maintain a progenitor cell population. These results support the use of seam cell development in C. elegans as a simple model system for studying stem and progenitor cell biology.

  9. Aggregate modeling of manufacturing systems

    NARCIS (Netherlands)

    Lefeber, A.A.J.; Armbruster, H.D.; Kempf, K.G.; Keskinocak, P.; Uzsoy, R.

    2011-01-01

    In this chapter we will present three approaches to model manufacturing systems in an aggregate way leading to fast and effective (i.e., scalable) simulations that allow the development of simulation tools for rapid exploration of different production scenarios in a factory as well as in a whole

  10. Ventilation system in fire modelization

    International Nuclear Information System (INIS)

    Cordero Garcia, S.

    2012-01-01

    There is a model of fire in an enclosure formed by two rooms. In one of them, it will cause the fire and check how the system of ventilation in different configurations responds. In addition, the behavior of selected targets, which will be a configuration of cables similar to those found in nuclear power stations will be analyzed.

  11. An extensible analysable system model

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, Rene Rydhof

    2008-01-01

    , this does not hold for real physical systems. Approaches such as threat modelling try to target the formalisation of the real-world domain, but still are far from the rigid techniques available in security research. Many currently available approaches to assurance of critical infrastructure security...

  12. Aggregate modeling of manufacturing systems

    NARCIS (Netherlands)

    Lefeber, A.A.J.; Armbruster, H.D.

    2007-01-01

    In this report we will present three approaches to model manufacturing systems in an aggregate way leading to fast and effective (i.e., scalable) simulations that allow the development of simulation tools for rapid exploration of different production scenarios in a factory as well as in a whole

  13. The RNAi Inheritance Machinery of Caenorhabditis elegans.

    Science.gov (United States)

    Spracklin, George; Fields, Brandon; Wan, Gang; Becker, Diveena; Wallig, Ashley; Shukla, Aditi; Kennedy, Scott

    2017-07-01

    Gene silencing mediated by dsRNA (RNAi) can persist for multiple generations in Caenorhabditis elegans (termed RNAi inheritance). Here we describe the results of a forward genetic screen in C. elegans that has identified six factors required for RNAi inheritance: GLH-1/VASA, PUP-1/CDE-1, MORC-1, SET-32, and two novel nematode-specific factors that we term here (heritable RNAi defective) HRDE-2 and HRDE-4 The new RNAi inheritance factors exhibit mortal germline (Mrt) phenotypes, which we show is likely caused by epigenetic deregulation in germ cells. We also show that HRDE-2 contributes to RNAi inheritance by facilitating the binding of small RNAs to the inheritance Argonaute (Ago) HRDE-1 Together, our results identify additional components of the RNAi inheritance machinery whose conservation provides insights into the molecular mechanism of RNAi inheritance, further our understanding of how the RNAi inheritance machinery promotes germline immortality, and show that HRDE-2 couples the inheritance Ago HRDE-1 with the small RNAs it needs to direct RNAi inheritance and germline immortality. Copyright © 2017 by the Genetics Society of America.

  14. Stochastic Modelling of Hydrologic Systems

    DEFF Research Database (Denmark)

    Jonsdottir, Harpa

    2007-01-01

    In this PhD project several stochastic modelling methods are studied and applied on various subjects in hydrology. The research was prepared at Informatics and Mathematical Modelling at the Technical University of Denmark. The thesis is divided into two parts. The first part contains...... an introduction and an overview of the papers published. Then an introduction to basic concepts in hydrology along with a description of hydrological data is given. Finally an introduction to stochastic modelling is given. The second part contains the research papers. In the research papers the stochastic methods...... are described, as at the time of publication these methods represent new contribution to hydrology. The second part also contains additional description of software used and a brief introduction to stiff systems. The system in one of the papers is stiff....

  15. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    after an oil spill. Engineering thermodynamics could be applied in the state-of-the-art sonar products through advanced artificial technology, if the speed of sound, solubility and density of oil-seawater systems could be satisfactorily modelled. The addition of methanol or glycols into unprocessed well...... is successfully applied to model the phase behaviour of water, chemical and hydrocarbon (oil) containing systems with newly developed pure component parameters for water and chemicals and characterization procedures for petroleum fluids. The performance of the PCSAFT EOS on liquid-liquid equilibria of water...... with hydrocarbons has been under debate for some vii years. An interactive step-wise procedure is proposed to fit the model parameters for small associating fluids by taking the liquid-liquid equilibrium data into account. It is still far away from a simple task to apply PC-SAFT in routine PVT simulations and phase...

  16. Functional phenotypic rescue of Caenorhabditis elegans neuroligin-deficient mutants by the human and rat NLGN1 genes.

    Directory of Open Access Journals (Sweden)

    Fernando Calahorro

    Full Text Available Neuroligins are cell adhesion proteins that interact with neurexins at the synapse. This interaction may contribute to differentiation, plasticity and specificity of synapses. In humans, single mutations in neuroligin encoding genes lead to autism spectrum disorder and/or mental retardation. Caenorhabditis elegans mutants deficient in nlg-1, an orthologue of human neuroligin genes, have defects in different behaviors. Here we show that the expression of human NLGN1 or rat Nlgn1 cDNAs in C. elegans nlg-1 mutants rescues the fructose osmotic strength avoidance and gentle touch response phenotypes. Two specific point mutations in NLGN3 and NLGN4 genes, involved in autistic spectrum disorder, were further characterized in this experimental system. The R451C allele described in NLGN3, was analyzed with both human NLGN1 (R453C and worm NLG-1 (R437C proteins, and both were not functional in rescuing the osmotic avoidance behavior and the gentle touch response phenotype. The D396X allele described in NLGN4, which produces a truncated protein, was studied with human NLGN1 (D432X and they did not rescue any of the behavioral phenotypes analyzed. In addition, RNAi feeding experiments measuring gentle touch response in wild type strain and worms expressing SID-1 in neurons (which increases the response to dsRNA, both fed with bacteria expressing dsRNA for nlg-1, provided evidence for a postsynaptic in vivo function of neuroligins both in muscle cells and neurons, equivalent to that proposed in mammals. This finding was further confirmed generating transgenic nlg-1 deficient mutants expressing NLG-1 under pan-neuronal (nrx-1 or pan-muscular (myo-3 specific promoters. All these results suggest that the nematode could be used as an in vivo model for studying particular synaptic mechanisms with proteins orthologues of humans involved in pervasive developmental disorders.

  17. Intrinsic JNK-MAPK pathway involvement requires daf-16-mediated immune response during Shigella flexneri infection in C. elegans.

    Science.gov (United States)

    Marudhupandiyan, Shanmugam; Balamurugan, Krishnaswamy

    2017-06-01

    The c-Jun N-terminal kinase-mitogen-activated protein kinase (JNK-MAPK) pathway assists in modulating signals for growth, survival, and metabolism, thereby coordinating many cellular events during normal and stress conditions. To understand the role of the JNK-MAPK pathway during bacterial infection, an in vivo model organism Caenorhabditis elegans was used. In order to check the involvement of the JNK-MAPK pathway, the survival rate of C. elegans wild type (WT), and JNK-MAPK pathway mutant worms' upon exposure to selective Gram-positive and Gram-negative pathogenic bacteria, was studied. Among the pathogens, Shigella flexneri M9OT was found to efficiently colonize inside the WT and JNK-MAPK pathway mutant worms. qPCR studies had suggested that the above pathway-specific genes kgb-2 and jnk-1 were prominently responsible for the immune response elicited by the host during the M9OT infection. In addition, daf-16, which is a major transcription factor of the insulin/insulin growth factor-1 signaling (IIS) pathway, was also found to be involved during the host response. Crosstalk between IIS and JNK-MAPK pathways has probably been involved in the activation of the host immune system, which consequently leads to lifespan extension. Furthermore, it is also observed that daf-16 activation by JNK-MAPK pathway leads to antimicrobial response, by activating lys-7 expression. These findings suggest that JNK-MAPK is not the sole pathway that enhances the immunity of the host. Nonetheless, the IIS pathway bridges the JNK-MAPK pathway that influences in protecting the host in counter to the M9OT infection.

  18. Morphology, ultrastructure, molecular phylogeny, and autecology of Euplotes elegans Kahl, 1932 (Hypotrichida; Euplotidae) isolated from the anoxic Mariager Fjord, Denmark.

    Science.gov (United States)

    Julian Schwarz, M V; Zuendorf, Alexandra; Stoeck, Thorsten

    2007-01-01

    The morphology, autecology, and molecular phylogeny of an euryhaline Euplotes isolate collected from the anoxic water column of the Mariager Fjord in Denmark were investigated. The isolate matches the original description of Euplotes elegans Kahl, 1932 very well. However, its dorsal silverline system is clearly distinct from the redescription of this species by Tuffrau. Thus, a neotypification is proposed for E. elegans Kahl, 1932. The oval-shaped cell has a mean size of 107 x 51 microm and is characterized by 9.4 dorsolateral kineties, seven prominent dorsal ridges, large elongated ampullae, which encircle the dorsal kinetids, 18 kinetids in the middorsal row, nine frontoventral cirri, five transversal cirri, and three caudal cirri (two right caudal cirri and one left marginal cirrus). The dorsal silverline system is of the double type with the narrow polygons located on the right side of the dorsal kinetids. The ecological tolerances of this species to pH, salinity, temperature, and oxygen match the ambient environmental conditions of the sampling site. Molecular phylogeny was studied using small subunit rRNA (SSU rRNA) gene sequences. The molecular data cluster E. elegans with Euplotes raikovi, a member of the Euplotopsis group. The data suggest that the E. elegans-E. raikovi clade represents an isolated and deep branch at the base of the Euplotes tree.

  19. Cotangent Models for Integrable Systems

    Science.gov (United States)

    Kiesenhofer, Anna; Miranda, Eva

    2017-03-01

    We associate cotangent models to a neighbourhood of a Liouville torus in symplectic and Poisson manifolds focusing on b-Poisson/ b-symplectic manifolds. The semilocal equivalence with such models uses the corresponding action-angle theorems in these settings: the theorem of Liouville-Mineur-Arnold for symplectic manifolds and an action-angle theorem for regular Liouville tori in Poisson manifolds (Laurent- Gengoux et al., IntMath Res Notices IMRN 8: 1839-1869, 2011). Our models comprise regular Liouville tori of Poisson manifolds but also consider the Liouville tori on the singular locus of a b-Poisson manifold. For this latter class of Poisson structures we define a twisted cotangent model. The equivalence with this twisted cotangent model is given by an action-angle theorem recently proved by the authors and Scott (Math. Pures Appl. (9) 105(1):66-85, 2016). This viewpoint of cotangent models provides a new machinery to construct examples of integrable systems, which are especially valuable in the b-symplectic case where not many sources of examples are known. At the end of the paper we introduce non-degenerate singularities as lifted cotangent models on b-symplectic manifolds and discuss some generalizations of these models to general Poisson manifolds.

  20. Graph modeling systems and methods

    Science.gov (United States)

    Neergaard, Mike

    2015-10-13

    An apparatus and a method for vulnerability and reliability modeling are provided. The method generally includes constructing a graph model of a physical network using a computer, the graph model including a plurality of terminating vertices to represent nodes in the physical network, a plurality of edges to represent transmission paths in the physical network, and a non-terminating vertex to represent a non-nodal vulnerability along a transmission path in the physical network. The method additionally includes evaluating the vulnerability and reliability of the physical network using the constructed graph model, wherein the vulnerability and reliability evaluation includes a determination of whether each terminating and non-terminating vertex represents a critical point of failure. The method can be utilized to evaluate wide variety of networks, including power grid infrastructures, communication network topologies, and fluid distribution systems.

  1. Natural lignans from Arctium lappa as antiaging agents in Caenorhabditis elegans.

    Science.gov (United States)

    Su, Shan; Wink, Michael

    2015-09-01

    Arctium lappa is a well-known traditional medicinal plant in China (TCM) and Europe that has been used for thousands of years to treat arthritis, baldness or cancer. The plant produces lignans as secondary metabolites, which have a wide range of bioactivities. Yet, their antiaging potential has not been explored. In this study, we isolated six lignans from A. lappa seeds, namely arctigenin, matairesinol, arctiin, (iso)lappaol A, lappaol C, and lappaol F. The antioxidant and antiaging properties of the isolated lignans were studied using Caenorhabditis elegans as a relevant animal model. All lignans at concentrations of 10 and 100 μM significantly extended the mean life span of C. elegans. The strongest effect was observed with matairesinol, which at a concentration of 100 μM extended the life span of worms by 25%. Additionally, we observed that five lignans are strong free radical-scavengers in vitro and in vivo and all lignans can improve survival of C. elegans under oxidative stress. Furthermore, the lignans can induce the nuclear translocation of the transcription factor DAF-16 and up-regulate its expression, suggesting that a possible underlying mechanism of the observed longevity-promoting activity of lignans depends on DAF-16 mediated signaling pathway. All lignans up-regulated the expression of jnk-1, indicating that lignans may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade. Our study reports new antiaging activities of lignans, which might be candidates for developing antiaging agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. A rolling circle replication mechanism produces multimeric lariats of mitochondrial DNA in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Samantha C Lewis

    2015-02-01

    Full Text Available Mitochondrial DNA (mtDNA encodes respiratory complex subunits essential to almost all eukaryotes; hence respiratory competence requires faithful duplication of this molecule. However, the mechanism(s of its synthesis remain hotly debated. Here we have developed Caenorhabditis elegans as a convenient animal model for the study of metazoan mtDNA synthesis. We demonstrate that C. elegans mtDNA replicates exclusively by a phage-like mechanism, in which multimeric molecules are synthesized from a circular template. In contrast to previous mammalian studies, we found that mtDNA synthesis in the C. elegans gonad produces branched-circular lariat structures with multimeric DNA tails; we were able to detect multimers up to four mtDNA genome unit lengths. Further, we did not detect elongation from a displacement-loop or analogue of 7S DNA, suggesting a clear difference from human mtDNA in regard to the site(s of replication initiation. We also identified cruciform mtDNA species that are sensitive to cleavage by the resolvase RusA; we suggest these four-way junctions may have a role in concatemer-to-monomer resolution. Overall these results indicate that mtDNA synthesis in C. elegans does not conform to any previously documented metazoan mtDNA replication mechanism, but instead are strongly suggestive of rolling circle replication, as employed by bacteriophages. As several components of the metazoan mitochondrial DNA replisome are likely phage-derived, these findings raise the possibility that the rolling circle mtDNA replication mechanism may be ancestral among metazoans.

  3. Heat-killed Lactobacillus spp. cells enhance survivals of Caenorhabditis elegans against Salmonella and Yersinia infections.

    Science.gov (United States)

    Lee, J; Choe, J; Kim, J; Oh, S; Park, S; Kim, S; Kim, Y

    2015-12-01

    This study examined the effect of feeding heat-killed Lactobacillus cells on the survival of Caenorhabditis elegans nematodes after Salmonella Typhimurium and Yersinia enterocolitica infection. The feeding of heat-killed Lactobacillus plantarum 133 (LP133) and Lactobacillus fermentum 21 (LP21) cells to nematodes was shown to significantly increase the survival rate as well as stimulate the expression of pmk-1 gene that key factor for C. elegans immunity upon infection compared with control nematodes that were only fed Escherichia coli OP50 (OP50) cells. These results suggest that heat-killed LP133 and LF21 cells exert preventive or protective effects against the Gram-negative bacteria Salm. Typhimurium and Y. enterocolitica. To better understand the mechanisms underlying the LF21-mediated and LP133-mediated protection against bacterial infection in nematodes, transcriptional profiling was performed for each experimental group. These experiments showed that genes related to energy generation and ageing, regulators of insulin/IGF-1-like signalling, DAF genes, oxidation and reduction processes, the defence response and/or the innate immune response, and neurological processes were upregulated in nematodes that had been fed heat-killed Lactobacillus cells compared with nematodes that had been fed E. coli cells. In this study, the feeding of heat-killed Lactobacillus bacteria to Caenorhabditis elegans nematodes was shown to decrease infection by Gram-negative bacteria and increase the host lifespan. C. elegans has a small, well-organized genome and is an excellent in vivo model organism; thus, these results will potentially shed light on important Lactobacillus-host interactions. © 2015 The Society for Applied Microbiology.

  4. Imaging C. elegans embryos using an epifluorescent microscope and open source software.

    Science.gov (United States)

    Verbrugghe, Koen J C; Chan, Raymond C

    2011-03-24

    Cellular processes, such as chromosome assembly, segregation and cytokinesis,are inherently dynamic. Time-lapse imaging of living cells, using fluorescent-labeled reporter proteins or differential interference contrast (DIC) microscopy, allows for the examination of the temporal progression of these dynamic events which is otherwise inferred from analysis of fixed samples(1,2). Moreover, the study of the developmental regulations of cellular processes necessitates conducting time-lapse experiments on an intact organism during development. The Caenorhabiditis elegans embryo is light-transparent and has a rapid, invariant developmental program with a known cell lineage(3), thus providing an ideal experiment model for studying questions in cell biology(4,5)and development(6-9). C. elegans is amendable to genetic manipulation by forward genetics (based on random mutagenesis(10,11)) and reverse genetics to target specific genes (based on RNAi-mediated interference and targeted mutagenesis(12-15)). In addition, transgenic animals can be readily created to express fluorescently tagged proteins or reporters(16,17). These traits combine to make it easy to identify the genetic pathways regulating fundamental cellular and developmental processes in vivo(18-21). In this protocol we present methods for live imaging of C. elegans embryos using DIC optics or GFP fluorescence on a compound epifluorescent microscope. We demonstrate the ease with which readily available microscopes, typically used for fixed sample imaging, can also be applied for time-lapse analysis using open-source software to automate the imaging process.

  5. Selection of reliable reference genes in Caenorhabditis elegans for analysis of nanotoxicity.

    Directory of Open Access Journals (Sweden)

    Yanqiong Zhang

    Full Text Available Despite rapid development and application of a wide range of manufactured metal oxide nanoparticles (NPs, the understanding of potential risks of using NPs is less completed, especially at the molecular level. The nematode Caenorhabditis elegans (C.elegans has been emerging as an environmental model to study the molecular mechanism of environmental contaminations, using standard genetic tools such as the real-time quantitative PCR (RT-qPCR. The most important factor that may affect the accuracy of RT-qPCR is to choose appropriate genes for normalization. In this study, we selected 13 reference gene candidates (act-1, cdc-42, pmp-3, eif-3.C, actin, act-2, csq-1, Y45F10D.4, tba-1, mdh-1, ama-1, F35G12.2, and rbd-1 to test their expression stability under different doses of nano-copper oxide (CuO 0, 1, 10, and 50 µg/mL using RT-qPCR. Four algorithms, geNorm, NormFinder, BestKeeper, and the comparative ΔCt method, were employed to evaluate these 13 candidates expressions. As a result, tba-1, Y45F10D.4 and pmp-3 were the most reliable, which may be used as reference genes in future study of nanoparticle-induced genetic response using C.elegans.

  6. Selection of reliable reference genes in Caenorhabditis elegans for analysis of nanotoxicity.

    Science.gov (United States)

    Zhang, Yanqiong; Chen, Dongliang; Smith, Michael A; Zhang, Baohong; Pan, Xiaoping

    2012-01-01

    Despite rapid development and application of a wide range of manufactured metal oxide nanoparticles (NPs), the understanding of potential risks of using NPs is less completed, especially at the molecular level. The nematode Caenorhabditis elegans (C.elegans) has been emerging as an environmental model to study the molecular mechanism of environmental contaminations, using standard genetic tools such as the real-time quantitative PCR (RT-qPCR). The most important factor that may affect the accuracy of RT-qPCR is to choose appropriate genes for normalization. In this study, we selected 13 reference gene candidates (act-1, cdc-42, pmp-3, eif-3.C, actin, act-2, csq-1, Y45F10D.4, tba-1, mdh-1, ama-1, F35G12.2, and rbd-1) to test their expression stability under different doses of nano-copper oxide (CuO 0, 1, 10, and 50 µg/mL) using RT-qPCR. Four algorithms, geNorm, NormFinder, BestKeeper, and the comparative ΔCt method, were employed to evaluate these 13 candidates expressions. As a result, tba-1, Y45F10D.4 and pmp-3 were the most reliable, which may be used as reference genes in future study of nanoparticle-induced genetic response using C.elegans.

  7. Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jitendra Kumar

    Full Text Available Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.

  8. Using Caenorhabditis elegans to Uncover Conserved Functions of Omega-3 and Omega-6 Fatty Acids

    Science.gov (United States)

    Watts, Jennifer L.

    2016-01-01

    The nematode Caenorhabditis elegans is a powerful model organism to study functions of polyunsaturated fatty acids. The ability to alter fatty acid composition with genetic manipulation and dietary supplementation permits the dissection of the roles of omega-3 and omega-6 fatty acids in many biological process including reproduction, aging and neurobiology. Studies in C. elegans to date have mostly identified overlapping functions of 20-carbon omega-6 and omega-3 fatty acids in reproduction and in neurons, however, specific roles for either omega-3 or omega-6 fatty acids are beginning to emerge. Recent findings with importance to human health include the identification of a conserved Cox-independent prostaglandin synthesis pathway, critical functions for cytochrome P450 derivatives of polyunsaturated fatty acids, the requirements for omega-6 and omega-3 fatty acids in sensory neurons, and the importance of fatty acid desaturation for long lifespan. Furthermore, the ability of C. elegans to interconvert omega-6 to omega-3 fatty acids using the FAT-1 omega-3 desaturase has been exploited in mammalian studies and biotechnology approaches to generate mammals capable of exogenous generation of omega-3 fatty acids. PMID:26848697

  9. Staphylococcus saprophyticus surface-associated protein (Ssp) is associated with lifespan reduction in Caenorhabditis elegans.

    Science.gov (United States)

    Szabados, Florian; Mohner, Amelie; Kleine, Britta; Gatermann, Sören G

    2013-10-01

    Staphylococcal lipases have been proposed as pathogenicity factors. In Staphylococcus saprophyticus the surface-associated protein (Ssp) has been previously characterized as a cell wall-associated true lipase. A S. saprophyticus Δssp::ermB mutant has been described as less virulent in an in vivo model of urinary tract infection compared with its wild-type. This is the first report showing that S. saprophyticus induced a lifespan reduction in Caenorhabditis elegans similar to that of S. aureus RN4220. In two S. saprophyticus Δssp::ermB mutants lifespan reduction in C. elegans was partly abolished. In order to attribute virulence to the lipase activity itself and distinguish this phenomenon from the presence of the Ssp-protein, the conserved active site of the lipase was modified by site-directed ligase-independent mutagenesis and lipase activity-deficient mutants were constructed. These results indicate that the Ssp is associated with pathogenicity in C. elegans and one could speculate that the lipase activity itself is responsible for this virulence.

  10. Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death.

    Science.gov (United States)

    Kirienko, Natalia V; Kirienko, Daniel R; Larkins-Ford, Jonah; Wählby, Carolina; Ruvkun, Gary; Ausubel, Frederick M

    2013-04-17

    The opportunistic pathogen Pseudomonas aeruginosa causes serious human infections, but effective treatments and the mechanisms mediating pathogenesis remain elusive. Caenorhabditis elegans shares innate immune pathways with humans, making it invaluable to investigate infection. To determine how P. aeruginosa disrupts host biology, we studied how P. aeruginosa kills C. elegans in a liquid-based pathogenesis model. We found that P. aeruginosa-mediated killing does not require quorum-sensing pathways or host colonization. A chemical genetic screen revealed that iron chelators alleviate P. aeruginosa-mediated killing. Consistent with a role for iron in P. aeruginosa pathogenesis, the bacterial siderophore pyoverdin was required for virulence and was sufficient to induce a hypoxic response and death in the absence of bacteria. Loss of the C. elegans hypoxia-inducing factor HIF-1, which regulates iron homeostasis, exacerbated P. aeruginosa pathogenesis, further linking hypoxia and killing. As pyoverdin is indispensable for virulence in mice, pyoverdin-mediated hypoxia is likely to be relevant in human pathogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

    Science.gov (United States)

    Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J.; Killilea, David W.; Kapahi, Pankaj

    2016-01-01

    Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. PMID:27078872

  12. Pollution by metals and toxicity assessment using Caenorhabditis elegans in sediments from the Magdalena River, Colombia

    International Nuclear Information System (INIS)

    Tejeda-Benitez, Lesly; Flegal, Russell; Odigie, Kingsley; Olivero-Verbel, Jesus

    2016-01-01

    The Magdalena River is the most important river in Colombia, supplying over 70% of the population of fish and drinking water, and it also is the main river transportation way of the country. It receives effluents from multiple sources along its course such as contaminant agricultural and industrial discharges. To evaluate the toxicity profile of Magdalena River sediments through endpoints such as survival, locomotion, and growth, wild type strains of Caenorhabditis elegans were exposed to aqueous extracts of the sediments. To identify changes in gene expression, GFP transgenic strains were used as reporter genes. Physiological and biochemical data were correlated with metal concentration in the sediments, identifying patterns of toxicity along the course of the river. Levels of some metals such as Cd, Cu, and Ni were above TEC and PEC limits. Effects in survival, growth, and locomotion were observed in most of the samples, and changes in gene expression were evident in the genes mtl-2, sod-4, and gst-1 using fluorescence expression. Cadmium and lead were the metals which were primarily associated with sediment toxicity, and the sampling sites with the highest increased expression of stress response genes were Barrancabermeja and Girardot. However, the diverse nature of toxic profiles observed in C. elegans in the study area showed the pervasiveness of different types of discharges throughout the river system. - Highlights: • The Magdalena River has high levels of some metals such as Cd, Cu, and Ni. • Most sediment extracts affected lethality, growth, and locomotion of C. elegans. • Sediment extracts induced expression changes in mtl-2, sod-4, and gst-1. • Sediment toxicity was primarily associated with Cd and Pb. • Highest toxicity was observed for samples collected in mining and industrial areas. - In Magdalena River sediments, Cd and Pb were associated with toxicity in Caenorhabditis elegans and expression of stress response genes were related to

  13. The C. elegans VAPB homolog VPR-1 is a permissive signal for gonad development.

    Science.gov (United States)

    Cottee, Pauline A; Cole, Tim; Schultz, Jessica; Hoang, Hieu D; Vibbert, Jack; Han, Sung Min; Miller, Michael A

    2017-06-15

    VAMP/synaptobrevin-associated proteins (VAPs) contain an N-terminal major sperm protein domain (MSPd) that is associated with amyotrophic lateral sclerosis. VAPs have an intracellular housekeeping function, as well as an extracellular signaling function mediated by the secreted MSPd. Here we show that the C. elegans VAP homolog VPR-1 is essential for gonad development. vpr-1 null mutants are maternal effect sterile due to arrested gonadogenesis following embryo hatching. Somatic gonadal precursor cells and germ cells fail to proliferate fully and complete their respective differentiation programs. Maternal or zygotic vpr-1 expression is sufficient to induce gonadogenesis and fertility. Genetic mosaic and cell type-specific expression studies indicate that vpr-1 activity is important in the nervous system, germ line and intestine. VPR-1 acts in parallel to Notch signaling, a key regulator of germline stem cell proliferation and differentiation. Neuronal vpr-1 expression is sufficient for gonadogenesis induction during a limited time period shortly after hatching. These results support the model that the secreted VPR-1 MSPd acts at least in part on gonadal sheath cell precursors in L1 to early L2 stage hermaphrodites to permit gonadogenesis. © 2017. Published by The Company of Biologists Ltd.

  14. The anti-aging and anti-oxidation effects of tea water extract in Caenorhabditis elegans.

    Science.gov (United States)

    Fei, Tianyi; Fei, Jian; Huang, Fang; Xie, Tianpei; Xu, Jifeng; Zhou, Yi; Yang, Ping

    2017-10-15

    Tea includes puer tea, black tea, green tea and many others. By using model organism Caenorhabditis elegans, the anti-aging and anti-oxidation effects of tea water extract were systemically examined in this study. We found that water extract of puer tea, black tea and green tea all increased the lifespan of worms, postponed Aβ-induced progressive paralysis in Alzheimer's disease transgenic worms, and improved the tolerance of worms to the oxidative stress induced by heavy metal Cr 6+ . Moreover, the anti-oxidation effects of tea water extract at low concentration were different among 4 kinds of brands of green tea. The underlying mechanisms were further explored using genetically manipulated-mutant worms. The anti-oxidative stress effects of green tea water extract depend on the dietary restriction and germline signaling pathways, but not the FOXO and mitochondrial respiratory chain signals. Therefore, tea water extract provides benefits of anti-aging, anti-AD and anti-oxidation. Copyright © 2017. Published by Elsevier Inc.

  15. Locomotion-learning behavior relationship in Caenorhabditis elegans following γ-ray irradiation

    International Nuclear Information System (INIS)

    Sakashita, Tetsuya; Hamada, Nobuyuki; Suzuki, Michiyo; Kobayashi, Yasuhiko; Ikeda, Daisuke D.; Yanase, Sumino; Ishii, Naoaki

    2008-01-01

    Learning impairment following ionizing radiation (IR) exposure is an important potential risk in manned space missions. We previously reported the modulatory effects of IR on salt chemotaxis learning in Caenorhabditis elegans. However, little is known about the effects of IR on the functional relationship in the nervous system. In the present study, we investigated the effects of γ-ray exposure on the relationship between locomotion and salt chemotaxis learning behavior. We found that effects of pre-learning irradiation on locomotion were significantly correlated with the salt chemotaxis learning performance, whereas locomotion was not directly related to chemotaxis to NaCl. On the other hand, locomotion was positively correlated with salt chemotaxis of animals which were irradiated during learning, and the correlation disappeared with increasing doses. These results suggest an indirect relationship between locomotion and salt chemotaxis learning in C. elegans, and that IR inhibits the innate relationship between locomotion and chemotaxis, which is related to salt chemotaxis learning conditioning of C. elegans. (author)

  16. Isoamyl alcohol odor promotes longevity and stress tolerance via DAF-16 in Caenorhabditis elegans.

    Science.gov (United States)

    Kurino, Chiho; Furuhashi, Tsubasa; Sudoh, Kaori; Sakamoto, Kazuichi

    2017-04-01

    The possibility that odor plays a role in lifespan regulation through effects on the nervous system is indicated by research on Caenorhabditis elegans. In fact, ablation of AWA and AWC, which are suggested as olfactory neurons, has been shown to extend lifespan via DAF-16, a homolog of FoxO. However, the effects of odor stimuli on the lifespan still remain unclear. Thus, we here aimed to clarify the effect of attractive and repulsive odors on longevity and stress tolerance in C. elegans and to analyze the pathways thereof. We used isoamyl alcohol as an attractive odor, and acetic acid as a repellent component, as identified by chemotaxis assay. We found that isoamyl alcohol stimulus promoted longevity in a DAF-16-dependent manner. On the other hand, acetic acid stimulus promoted thermotolerance through mechanisms independent of DAF-16. Above all, our results indicate that odor stimuli affect the lifespan and stress tolerance of C. elegans, with attractive and repulsive odors exerting their effects through different mechanisms, and that longevity is induced by both activation and inactivation of olfactory neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Dafachronic acid inhibits C. elegans germ cell proliferation in a DAF-12-dependent manner.

    Science.gov (United States)

    Mukherjee, Madhumati; Chaudhari, Snehal N; Balachandran, Riju S; Vagasi, Alexandra S; Kipreos, Edward T

    2017-12-15

    Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites. Using a C. elegans germ cell primary culture system, we show that DA inhibits the proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large tumors in adult tumorous germline mutants and decreases the proliferation of wild-type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable effect on the proliferation of larval-stage germ cells in wild type. The inhibition of adult germ cell proliferation by DA requires its canonical receptor DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9 increases germ cell proliferation in wild-type adult hermaphrodites and the frequency of large tumors in germline tumorous mutants, suggesting that DA inhibits the rate of germ cell proliferation under normal growth conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Discrete modelling of drapery systems

    Science.gov (United States)

    Thoeni, Klaus; Giacomini, Anna

    2016-04-01

    Drapery systems are an efficient and cost-effective measure in preventing and controlling rockfall hazards on rock slopes. The simplest form consists of a row of ground anchors along the top of the slope connected to a horizontal support cable from which a wire mesh is suspended down the face of the slope. Such systems are generally referred to as simple or unsecured draperies (Badger and Duffy 2012). Variations such as secured draperies, where a pattern of ground anchors is incorporated within the field of the mesh, and hybrid systems, where the upper part of an unsecured drapery is elevated to intercept rockfalls originating upslope of the installation, are becoming more and more popular. This work presents a discrete element framework for simulation of unsecured drapery systems and its variations. The numerical model is based on the classical discrete element method (DEM) and implemented into the open-source framework YADE (Šmilauer et al., 2010). The model takes all relevant interactions between block, drapery and slope into account (Thoeni et al., 2014) and was calibrated and validated based on full-scale experiments (Giacomini et al., 2012).The block is modelled as a rigid clump made of spherical particles which allows any shape to be approximated. The drapery is represented by a set of spherical particle with remote interactions. The behaviour of the remote interactions is governed by the constitutive behaviour of the wire and generally corresponds to a piecewise linear stress-strain relation (Thoeni et al., 2013). The same concept is used to model wire ropes. The rock slope is represented by rigid triangular elements where material properties (e.g., normal coefficient of restitution, friction angle) are assigned to each triangle. The capabilities of the developed model to simulate drapery systems and estimate the residual hazard involved with such systems is shown. References Badger, T.C., Duffy, J.D. (2012) Drapery systems. In: Turner, A.K., Schuster R

  19. Quantum models of classical systems

    International Nuclear Information System (INIS)

    Hájíček, P

    2015-01-01

    Quantum statistical methods that are commonly used for the derivation of classical thermodynamic properties are extended to classical mechanical properties. The usual assumption that every real motion of a classical mechanical system is represented by a sharp trajectory is not testable and is replaced by a class of fuzzy models, the so-called maximum entropy (ME) packets. The fuzzier are the compared classical and quantum ME packets, the better seems to be the match between their dynamical trajectories. Classical and quantum models of a stiff rod will be constructed to illustrate the resulting unified quantum theory of thermodynamic and mechanical properties. (paper)

  20. Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Roz Laing

    Full Text Available The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid

  1. Osmotic potential of Zinnia elegans plant material affects the yield ...

    African Journals Online (AJOL)

    Jane

    2010-12-20

    Dec 20, 2010 ... The Zinnia elegans cell suspension culture is excellent for ... development and therefore dimensions of TEs in an in vitro .... Electrical conductivity and light intensity effects on ..... cell wall formation in the woody dicot stem.

  2. Quantitative proteomics by amino acid labeling in C. elegans

    DEFF Research Database (Denmark)

    Fredens, Julius; Engholm-Keller, Kasper; Giessing, Anders

    2011-01-01

    We demonstrate labeling of Caenorhabditis elegans with heavy isotope-labeled lysine by feeding them with heavy isotope-labeled Escherichia coli. Using heavy isotope-labeled worms and quantitative proteomics methods, we identified several proteins that are regulated in response to loss or RNAi-med......-mediated knockdown of the nuclear hormone receptor 49 in C. elegans. The combined use of quantitative proteomics and selective gene knockdown is a powerful tool for C. elegans biology.......We demonstrate labeling of Caenorhabditis elegans with heavy isotope-labeled lysine by feeding them with heavy isotope-labeled Escherichia coli. Using heavy isotope-labeled worms and quantitative proteomics methods, we identified several proteins that are regulated in response to loss or RNAi...

  3. An automated microfluidic multiplexer for fast delivery of C. elegans populations from multiwells.

    Directory of Open Access Journals (Sweden)

    Navid Ghorashian

    Full Text Available Automated biosorter platforms, including recently developed microfluidic devices, enable and accelerate high-throughput and/or high-resolution bioassays on small animal models. However, time-consuming delivery of different organism populations to these systems introduces a major bottleneck to executing large-scale screens. Current population delivery strategies rely on suction from conventional well plates through tubing periodically exposed to air, leading to certain disadvantages: 1 bubble introduction to the sample, interfering with analysis in the downstream system, 2 substantial time drain from added bubble-cleaning steps, and 3 the need for complex mechanical systems to manipulate well plate position. To address these concerns, we developed a multiwell-format microfluidic platform that can deliver multiple distinct animal populations from on-chip wells using multiplexed valve control. This Population Delivery Chip could operate autonomously as part of a relatively simple setup that did not require any of the major mechanical moving parts typical of plate-handling systems to address a given well. We demonstrated automatic serial delivery of 16 distinct C. elegans worm populations to a single outlet without introducing any bubbles to the samples, causing cross-contamination, or damaging the animals. The device achieved delivery of more than 90% of the population preloaded into a given well in 4.7 seconds; an order of magnitude faster than delivery modalities in current use. This platform could potentially handle other similarly sized model organisms, such as zebrafish and drosophila larvae or cellular micro-colonies. The device's architecture and microchannel dimensions allow simple expansion for processing larger numbers of populations.

  4. Models of the venous system

    DEFF Research Database (Denmark)

    Mehlsen, J

    2000-01-01

    Cardiac output is largely controlled by venous return, the driving force of which is the energy remaining at the postcapillary venous site. This force is influenced by forces acting close to the right atrium, and internally or externally upon the veins along their course. Analogue models of the v......Cardiac output is largely controlled by venous return, the driving force of which is the energy remaining at the postcapillary venous site. This force is influenced by forces acting close to the right atrium, and internally or externally upon the veins along their course. Analogue models...... of the venous system require at least three elements: a resistor, a capacitor and an inductor, with the latter being of more importance in the venous than in the arterial system. Non-linearities must be considered in pressure/flow relations in the small venules, during venous collapse, or low flow conditions...

  5. Studies of Catalytic Model Systems

    DEFF Research Database (Denmark)

    Holse, Christian

    The overall topic of this thesis is within the field of catalysis, were model systems of different complexity have been studied utilizing a multipurpose Ultra High Vacuum chamber (UHV). The thesis falls in two different parts. First a simple model system in the form of a ruthenium single crystal...... of the Cu/ZnO nanoparticles is highly relevant to industrial methanol synthesis for which the direct interaction of Cu and ZnO nanocrystals synergistically boost the catalytic activity. The dynamical behavior of the nanoparticles under reducing and oxidizing environments were studied by means of ex situ X......-ray Photoelectron Electron Spectroscopy (XPS) and in situ Transmission Electron Microscopy (TEM). The surface composition of the nanoparticles changes reversibly as the nanoparticles exposed to cycles of high-pressure oxidation and reduction (200 mbar). Furthermore, the presence of metallic Zn is observed by XPS...

  6. Aerial Measuring System Sensor Modeling

    International Nuclear Information System (INIS)

    Detwiler, R.S.

    2002-01-01

    This project deals with the modeling the Aerial Measuring System (AMS) fixed-wing and rotary-wing sensor systems, which are critical U.S. Department of Energy's National Nuclear Security Administration (NNSA) Consequence Management assets. The fixed-wing system is critical in detecting lost or stolen radiography or medical sources, or mixed fission products as from a commercial power plant release at high flying altitudes. The helicopter is typically used at lower altitudes to determine ground contamination, such as in measuring americium from a plutonium ground dispersal during a cleanup. Since the sensitivity of these instruments as a function of altitude is crucial in estimating detection limits of various ground contaminations and necessary count times, a characterization of their sensitivity as a function of altitude and energy is needed. Experimental data at altitude as well as laboratory benchmarks is important to insure that the strong effects of air attenuation are modeled correctly. The modeling presented here is the first attempt at such a characterization of the equipment for flying altitudes. The sodium iodide (NaI) sensors utilized with these systems were characterized using the Monte Carlo N-Particle code (MCNP) developed at Los Alamos National Laboratory. For the fixed wing system, calculations modeled the spectral response for the 3-element NaI detector pod and High-Purity Germanium (HPGe) detector, in the relevant energy range of 50 keV to 3 MeV. NaI detector responses were simulated for both point and distributed surface sources as a function of gamma energy and flying altitude. For point sources, photopeak efficiencies were calculated for a zero radial distance and an offset equal to the altitude. For distributed sources approximating an infinite plane, gross count efficiencies were calculated and normalized to a uniform surface deposition of 1 microCi/m 2 . The helicopter calculations modeled the transport of americium-241 ( 241 Am) as this is

  7. rBTI reduced β-amyloid-induced toxicity by promoting autophagy-lysosomal degradation via DAF-16 in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Jiao; Cui, Xiaodong; Ma, Xiaoli; Wang, Zhuanhua

    2017-03-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disease, of which β-amyloid (Aβ) induced toxicity was suggested as a main cause. Some substances with prolongevity effects have been shown to be protective against AD. In a previous study we demonstrated that a recombinant buckwheat trypsin inhibitor (rBTI) could prolonge the lifespan in Caenorhabditis elegans (C. elegans). Here, we investigated whether rBTI may benefit to mitigate the AD symptom by feeding the AD model C. elegans CL4176. CL4176 is a transgenic C. elegans expressing human Aβ 3-42 in muscle tissue. The results showed that rBTI not only could extend lifespan but also could reduce Aβ toxicity-triggered body paralysis in AD worms. Further study found the accumulation of Aβ was decreased and autophagy-lysosomal degradation pathway was activated in AD worms treated with rBTI. Moreover, the inhibition of autophagy reduced rBTI-mediated paralysis delay. Genetic analyses showed rBTI increased the transcriptional activity of dauer formation abnormal-16 (DAF-16) and the disruption of daf-16 abolished rBTI-mediated protective effect in AD worms. Taken together, these data indicated that rBTI promoted the autophagy-lysosomal degradation pathway to reduce the Aβ-induced toxicity via DAF-16 in an AD model C. elegans, implying that BTI has the potential to protect against AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Modeling fuel cell stack systems

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J H [Los Alamos National Lab., Los Alamos, NM (United States); Lalk, T R [Dept. of Mech. Eng., Texas A and M Univ., College Station, TX (United States)

    1998-06-15

    A technique for modeling fuel cell stacks is presented along with the results from an investigation designed to test the validity of the technique. The technique was specifically designed so that models developed using it can be used to determine the fundamental thermal-physical behavior of a fuel cell stack for any operating and design configuration. Such models would be useful tools for investigating fuel cell power system parameters. The modeling technique can be applied to any type of fuel cell stack for which performance data is available for a laboratory scale single cell. Use of the technique is demonstrated by generating sample results for a model of a Proton Exchange Membrane Fuel Cell (PEMFC) stack consisting of 125 cells each with an active area of 150 cm{sup 2}. A PEMFC stack was also used in the verification investigation. This stack consisted of four cells, each with an active area of 50 cm{sup 2}. Results from the verification investigation indicate that models developed using the technique are capable of accurately predicting fuel cell stack performance. (orig.)

  9. Model reduction of parametrized systems

    CERN Document Server

    Ohlberger, Mario; Patera, Anthony; Rozza, Gianluigi; Urban, Karsten

    2017-01-01

    The special volume offers a global guide to new concepts and approaches concerning the following topics: reduced basis methods, proper orthogonal decomposition, proper generalized decomposition, approximation theory related to model reduction, learning theory and compressed sensing, stochastic and high-dimensional problems, system-theoretic methods, nonlinear model reduction, reduction of coupled problems/multiphysics, optimization and optimal control, state estimation and control, reduced order models and domain decomposition methods, Krylov-subspace and interpolatory methods, and applications to real industrial and complex problems. The book represents the state of the art in the development of reduced order methods. It contains contributions from internationally respected experts, guaranteeing a wide range of expertise and topics. Further, it reflects an important effor t, carried out over the last 12 years, to build a growing research community in this field. Though not a textbook, some of the chapters ca...

  10. Component Reification in Systems Modelling

    DEFF Research Database (Denmark)

    Bendisposto, Jens; Hallerstede, Stefan

    When modelling concurrent or distributed systems in Event-B, we often obtain models where the structure of the connected components is specified by constants. Their behaviour is specified by the non-deterministic choice of event parameters for events that operate on shared variables. From a certain......? These components may still refer to shared variables. Events of these components should not refer to the constants specifying the structure. The non-deterministic choice between these components should not be via parameters. We say the components are reified. We need to address how the reified components get...... reflected into the original model. This reflection should indicate the constraints on how to connect the components....

  11. Computational models of complex systems

    CERN Document Server

    Dabbaghian, Vahid

    2014-01-01

    Computational and mathematical models provide us with the opportunities to investigate the complexities of real world problems. They allow us to apply our best analytical methods to define problems in a clearly mathematical manner and exhaustively test our solutions before committing expensive resources. This is made possible by assuming parameter(s) in a bounded environment, allowing for controllable experimentation, not always possible in live scenarios. For example, simulation of computational models allows the testing of theories in a manner that is both fundamentally deductive and experimental in nature. The main ingredients for such research ideas come from multiple disciplines and the importance of interdisciplinary research is well recognized by the scientific community. This book provides a window to the novel endeavours of the research communities to present their works by highlighting the value of computational modelling as a research tool when investigating complex systems. We hope that the reader...

  12. Models of hot stellar systems

    International Nuclear Information System (INIS)

    Van Albada, T.S.

    1986-01-01

    Elliptical galaxies consist almost entirely of stars. Sites of recent star formation are rare, and most stars are believed to be several billion years old, perhaps as old as the Universe itself (--10/sup 10/ yrs). Stellar motions in ellipticals show a modest amount of circulation about the center of the system, but most support against the force of gravity is provided by random motions; for this reason ellipticals are called 'hot' stellar systems. Spiral galaxies usually also contain an appreciable amount of gas (--10%, mainly atomic hydrogen) and new stars are continually being formed out of this gas, especially in the spiral arms. In contrast to ellipticals, support against gravity in spiral galaxies comes almost entirely from rotation; random motions of the stars with respect to rotation are small. Consequently, spiral galaxies are called 'cold' stellar systems. Other than in hot systems, in cold systems the collective response of stars to variations in the force field is an essential part of the dynamics. The present overview is limited to mathematical models of hot systems. Computational methods are also discussed

  13. Aerial measuring system sensor modeling

    International Nuclear Information System (INIS)

    Detwiler, Rebecca

    2002-01-01

    The AMS fixed-wing and rotary-wing systems are critical National Nuclear Security Administration (NNSA) Emergency Response assets. This project is principally focused on the characterization of the sensors utilized with these systems via radiation transport calculations. The Monte Carlo N-Particle code (MCNP) which has been developed at Los Alamos National Laboratory was used to model the detector response of the AMS fixed wing and helicopter systems. To validate the calculations, benchmark measurements were made for simple source-detector configurations. The fixed-wing system is an important tool in response to incidents involving the release of mixed fission products (a commercial power reactor release), the threat or actual explosion of a Radiological Dispersal Device, and the loss or theft of a large industrial source (a radiography source). Calculations modeled the spectral response for the sensors contained, a 3-element NaI detector pod and HpGe detector, in the relevant energy range of 50 keV to 3 MeV. NaI detector responses were simulated for both point and distributed surface sources as a function of gamma energy and flying altitude. For point sources, photo-peak efficiencies were calculated for a zero radial distance and an offset equal to the altitude. For distributed sources approximating infinite plane, gross count efficiencies were calculated and normalized to a uniform surface deposition of 1 C i/m2

  14. Evolution of outcrossing in experimental populations of Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Henrique Teotonio

    Full Text Available Caenorhabditis elegans can reproduce exclusively by self-fertilization. Yet, males can be maintained in laboratory populations, a phenomenon that continues to puzzle biologists. In this study we evaluated the role of males in facilitating adaptation to novel environments. For this, we contrasted the evolution of a fitness component exclusive to outcrossing in experimental populations of different mating systems. We introgressed a modifier of outcrossing into a hybrid population derived from several wild isolates to transform the wild-type androdioecious mating system into a dioecious mating system. By genotyping 375 single-nucleotide polymorphisms we show that the two populations had similar standing genetic diversity available for adaptation, despite the occurrence of selection during their derivation. We then performed replicated experimental evolution under the two mating systems from starting conditions of either high or low levels of diversity, under defined environmental conditions of discrete non-overlapping generations, constant density at high population sizes (N = 10(4, no obvious spatial structure and abundant food resources. During 100 generations measurements of sex ratios and male competitive performance showed: 1 adaptation to the novel environment; 2 directional selection on male frequency under androdioecy; 3 optimal outcrossing rates of 0.5 under androdioecy; 4 the existence of initial inbreeding depression; and finally 5 that the strength of directional selection on male competitive performance does not depend on male frequencies. Taken together, these results suggest that androdioecious males are maintained at intermediate frequencies because outcrossing is adaptive.

  15. Validation of Embedded System Verification Models

    NARCIS (Netherlands)

    Marincic, J.; Mader, Angelika H.; Wieringa, Roelf J.

    The result of a model-based requirements verification shows that the model of a system satisfies (or not) formalised system requirements. The verification result is correct only if the model represents the system adequately. No matter what modelling technique we use, what precedes the model

  16. The Shift of the Intestinal Microbiome in the Innate Immunity-Deficient Mutant rde-1 Strain of C. elegans upon Orsay Virus Infection

    Directory of Open Access Journals (Sweden)

    Yuanyuan Guo

    2017-05-01

    Full Text Available The status of intestinal microbiota is a determinant of host health. However, the alteration of the gut microbiota caused by the innate immune response to virus infection is unclear. Caenorhabditis elegans and its natural virus Orsay provide an excellent model of host–virus interactions. We evaluated the intestinal microbial community complexity of the wild-type N2 and the innate immunity-deficient mutant rde-1 (ne219 strains of C. elegans upon Orsay virus infection. The gut microbiota diversity was decreased in rde-1 (ne219 mutant animals, and a large number of genes were associated with the difference between infected and uninfected rde-1 (ne219 mutant animals. Therefore, this study provides the first evaluation of the alterations caused by Orsay virus on intestinal microbiota in wildtype and innate immunity-deficient animals using C. elegans as the model species. Our findings indicate that virus infection may alters the microbiome in animals with defective immune response.

  17. The Shift of the Intestinal Microbiome in the Innate Immunity-Deficient Mutant rde-1 Strain of C. elegans upon Orsay Virus Infection.

    Science.gov (United States)

    Guo, Yuanyuan; Xun, Zhe; Coffman, Stephanie R; Chen, Feng

    2017-01-01

    The status of intestinal microbiota is a determinant of host health. However, the alteration of the gut microbiota caused by the innate immune response to virus infection is unclear. Caenorhabditis elegans and its natural virus Orsay provide an excellent model of host-virus interactions. We evaluated the intestinal microbial community complexity of the wild-type N2 and the innate immunity-deficient mutant rde-1 ( ne219 ) strains of C. elegans upon Orsay virus infection. The gut microbiota diversity was decreased in rde-1 ( ne219 ) mutant animals, and a large number of genes were associated with the difference between infected and uninfected rde-1 ( ne219 ) mutant animals. Therefore, this study provides the first evaluation of the alterations caused by Orsay virus on intestinal microbiota in wildtype and innate immunity-deficient animals using C. elegans as the model species. Our findings indicate that virus infection may alters the microbiome in animals with defective immune response.

  18. Mathematical Modeling of Constrained Hamiltonian Systems

    NARCIS (Netherlands)

    Schaft, A.J. van der; Maschke, B.M.

    1995-01-01

    Network modelling of unconstrained energy conserving physical systems leads to an intrinsic generalized Hamiltonian formulation of the dynamics. Constrained energy conserving physical systems are directly modelled as implicit Hamiltonian systems with regard to a generalized Dirac structure on the

  19. A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods.

    Directory of Open Access Journals (Sweden)

    Kelvin Yen

    Full Text Available The nematode Caenorhabditis elegans has been employed as a model organism to study human obesity due to the conservation of the pathways that regulate energy metabolism. To assay for fat storage in C. elegans, a number of fat-soluble dyes have been employed including BODIPY, Nile Red, Oil Red O, and Sudan Black. However, dye-labeled assays produce results that often do not correlate with fat stores in C. elegans. An alternative label-free approach to analyze fat storage in C. elegans has recently been described with coherent anti-Stokes Raman scattering (CARS microscopy. Here, we compare the performance of CARS microscopy with standard dye-labeled techniques and biochemical quantification to analyze fat storage in wild type C. elegans and with genetic mutations in the insulin/IGF-1 signaling pathway including the genes daf-2 (insulin/IGF-1 receptor, rict-1 (rictor and sgk-1 (serum glucocorticoid kinase. CARS imaging provides a direct measure of fat storage with unprecedented details including total fat stores as well as the size, number, and lipid-chain unsaturation of individual lipid droplets. In addition, CARS/TPEF imaging reveals a neutral lipid species that resides in both the hypodermis and the intestinal cells and an autofluorescent organelle that resides exclusively in the intestinal cells. Importantly, coherent addition of the CARS fields from the C-H abundant neutral lipid permits selective CARS imaging of the fat store, and further coupling of spontaneous Raman analysis provides unprecedented details including lipid-chain unsaturation of individual lipid droplets. We observe that although daf-2, rict-1, and sgk-1 mutants affect insulin/IGF-1 signaling, they exhibit vastly different phenotypes in terms of neutral lipid and autofluorescent species. We find that CARS imaging gives quantification similar to standard biochemical triglyceride quantification. Further, we independently confirm that feeding worms with vital dyes does not lead

  20. Cognitive models embedded in system simulation models

    International Nuclear Information System (INIS)

    Siegel, A.I.; Wolf, J.J.

    1982-01-01

    If we are to discuss and consider cognitive models, we must first come to grips with two questions: (1) What is cognition; (2) What is a model. Presumably, the answers to these questions can provide a basis for defining a cognitive model. Accordingly, this paper first places these two questions into perspective. Then, cognitive models are set within the context of computer simulation models and a number of computer simulations of cognitive processes are described. Finally, pervasive issues are discussed vis-a-vis cognitive modeling in the computer simulation context

  1. Modelling of data acquisition systems

    International Nuclear Information System (INIS)

    Buono, S.; Gaponenko, I.; Jones, R.; Mapelli, L.; Mornacchi, G.; Prigent, D.; Sanchez-Corral, E.; Spiwoks, R.; Skiadelli, M.; Ambrosini, G.

    1994-01-01

    The RD13 project was approved in April 1991 for the development of a scalable data taking system suitable to host various LHC studies. One of its goals is to use simulations as a tool for understanding, evaluating, and constructing different configurations of such data acquisition (DAQ) systems. The RD13 project has developed a modelling framework for this purpose. It is based on MODSIM II, an object-oriented, discrete-event simulation language. A library of DAQ components allows to describe a variety of DAQ architectures and different hardware options in a modular and scalable way. A graphical user interface (GUI) is used to do easy configuration, initialization and on-line monitoring of the simulation program. A tracing facility is used to do flexible off-line analysis of a trace file written at run-time

  2. Characterization of N-acyl phosphatidylethanolamine-specific phospholipase-D isoforms in the nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Neale Harrison

    Full Text Available N-acylethanolamines are an important class of lipid signaling molecules found in many species, including the nematode Caenorhabditis elegans (C. elegans where they are involved in development and adult lifespan. In mammals, the relative activity of the biosynthetic enzyme N-acyl phosphatidylethanolamine-specific phospholipase-D and the hydrolytic enzyme fatty acid amide hydrolase determine N-acylethanolamine levels. C. elegans has two N-acyl phosphatidylethanolamine-specific phospholipase-D orthologs, nape-1 and nape-2, that are likely to have arisen from a gene duplication event. Here, we find that recombinant C. elegans NAPE-1 and NAPE-2 are capable of generating N-acylethanolamines in vitro, confirming their functional conservation. In vivo, they exhibit overlapping expression in the pharynx and the nervous system, but are also expressed discretely in these and other tissues, suggesting divergent roles. Indeed, nape-1 over-expression results in delayed growth and shortened lifespan only at 25°C, while nape-2 over-expression results in significant larval arrest and increased adult lifespan at 15°C. Interestingly, deletion of the N-acylethanolamine degradation enzyme faah-1 exacerbates nape-1 over-expression phenotypes, but suppresses the larval arrest phenotype of nape-2 over-expression, suggesting that faah-1 is coupled to nape-2, but not nape-1, in a negative feedback loop. We also find that over-expression of either nape-1 or nape-2 significantly enhances recovery from the dauer larval stage in the insulin signaling mutant daf-2(e1368, but only nape-1 over-expression reduces daf-2 adult lifespan, consistent with increased levels of the N-acylethanolamine eicosapentaenoyl ethanolamine. These results provide evidence that N-acylethanolamine biosynthetic enzymes in C. elegans have conserved function and suggest a temperature-dependent, functional divergence between the two isoforms.

  3. Environmental CO2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

    Science.gov (United States)

    Fenk, Lorenz A.; de Bono, Mario

    2015-01-01

    Carbon dioxide (CO2) gradients are ubiquitous and provide animals with information about their environment, such as the potential presence of prey or predators. The nematode Caenorhabditis elegans avoids elevated CO2, and previous work identified three neuron pairs called “BAG,” “AFD,” and “ASE” that respond to CO2 stimuli. Using in vivo Ca2+ imaging and behavioral analysis, we show that C. elegans can detect CO2 independently of these sensory pathways. Many of the C. elegans sensory neurons we examined, including the AWC olfactory neurons, the ASJ and ASK gustatory neurons, and the ASH and ADL nociceptors, respond to a rise in CO2 with a rise in Ca2+. In contrast, glial sheath cells harboring the sensory endings of C. elegans’ major chemosensory neurons exhibit strong and sustained decreases in Ca2+ in response to high CO2. Some of these CO2 responses appear to be cell intrinsic. Worms therefore may couple detection of CO2 to that of other cues at the earliest stages of sensory processing. We show that C. elegans persistently suppresses oviposition at high CO2. Hermaphrodite-specific neurons (HSNs), the executive neurons driving egg-laying, are tonically inhibited when CO2 is elevated. CO2 modulates the egg-laying system partly through the AWC olfactory neurons: High CO2 tonically activates AWC by a cGMP-dependent mechanism, and AWC output inhibits the HSNs. Our work shows that CO2 is a more complex sensory cue for C. elegans than previously thought, both in terms of behavior and neural circuitry. PMID:26100886

  4. Spontaneous Age-Related Neurite Branching in C. elegans

    Science.gov (United States)

    Tank, Elizabeth M. H.; Rodgers, Kasey E.; Kenyon, Cynthia

    2011-01-01

    The analysis of morphological changes that occur in the nervous system during normal aging could provide insight into cognitive decline and neurodegenerative disease. Previous studies have suggested that the nervous system of C. elegans maintains its structural integrity with age despite the deterioration of surrounding tissues. Unexpectedly, we observed that neurons in aging animals frequently displayed ectopic branches, and that the prevalence of these branches increased with time. Within age-matched populations, the branching of mechnosensory neurons correlated with decreased response to light touch and decreased mobility. The incidence of branching was influenced by two pathways that can affect the rate of aging, the Jun kinase pathway and the insulin/IGF-1 pathway. Loss of Jun kinase signaling, which slightly shortens lifespan, dramatically increased and accelerated the frequency of neurite branching. Conversely, inhibition of the daf-2 insulin/IGF-1-like signaling pathway, which extends lifespan, delayed and suppressed branching, and this delay required DAF-16/FOXO activity. Both JNK-1 and DAF-16 appeared to act within neurons in a cell-autonomous manner to influence branching, and, through their tissue-specific expression, it was possible to disconnect the rate at which branching occurred from the overall rate of aging of the animal. Old age has generally been associated with the decline and deterioration of different tissues, except in the case of tumor cell growth. To our knowledge, this is the first indication that aging can potentiate another form of growth, the growth of neurite branches, in normal animals. PMID:21697377

  5. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

    2003-01-01

    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering

  6. Bond graph modeling of centrifugal compression systems

    OpenAIRE

    Uddin, Nur; Gravdahl, Jan Tommy

    2015-01-01

    A novel approach to model unsteady fluid dynamics in a compressor network by using a bond graph is presented. The model is intended in particular for compressor control system development. First, we develop a bond graph model of a single compression system. Bond graph modeling offers a different perspective to previous work by modeling the compression system based on energy flow instead of fluid dynamics. Analyzing the bond graph model explains the energy flow during compressor surge. Two pri...

  7. A model management system for combat simulation

    OpenAIRE

    Dolk, Daniel R.

    1986-01-01

    The design and implementation of a model management system to support combat modeling is discussed. Structured modeling is introduced as a formalism for representing mathematical models. A relational information resource dictionary system is developed which can accommodate structured models. An implementation is described. Structured modeling is then compared to Jackson System Development (JSD) as a methodology for facilitating discrete event simulation. JSD is currently better at representin...

  8. Quantitative proteomics by amino acid labeling identifies novel NHR-49 regulated proteins in C. elegans

    DEFF Research Database (Denmark)

    Fredens, Julius; Færgeman, Nils J.

    2012-01-01

    in the nematode Caenorhabditis elegans. We have recently shown that C. elegans can be completely labeled with heavy-labeled lysine by feeding worms on prelabeled lysine auxotroph Escherichia coli for just one generation. We applied this methodology to examine the organismal response to functional loss or RNAi...... gene knockdown by RNAi provides a powerful tool with broad implications for C. elegans biology....

  9. Model Driven Development of Data Sensitive Systems

    DEFF Research Database (Denmark)

    Olsen, Petur

    2014-01-01

    storage systems, where the actual values of the data is not relevant for the behavior of the system. For many systems the values are important. For instance the control flow of the system can be dependent on the input values. We call this type of system data sensitive, as the execution is sensitive...... to the values of variables. This theses strives to improve model-driven development of such data-sensitive systems. This is done by addressing three research questions. In the first we combine state-based modeling and abstract interpretation, in order to ease modeling of data-sensitive systems, while allowing...... efficient model-checking and model-based testing. In the second we develop automatic abstraction learning used together with model learning, in order to allow fully automatic learning of data-sensitive systems to allow learning of larger systems. In the third we develop an approach for modeling and model-based...

  10. Serotonergic Chemosensory Neurons Modify the C. elegans Immune Response by Regulating G-Protein Signaling in Epithelial Cells

    Science.gov (United States)

    Anderson, Alexandra; Laurenson-Schafer, Henry; Partridge, Frederick A.; Hodgkin, Jonathan; McMullan, Rachel

    2013-01-01

    The nervous and immune systems influence each other, allowing animals to rapidly protect themselves from changes in their internal and external environment. However, the complex nature of these systems in mammals makes it difficult to determine how neuronal signaling influences the immune response. Here we show that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons, modulates the immune response. Serotonin released from these cells acts, directly or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in these cells is required for the immune response to infection by the natural pathogen Microbacterium nematophilum. Here we show that serotonin signaling suppresses the innate immune response and limits the rate of pathogen clearance. We show that C. elegans uses classical neurotransmitters to alter the immune response. Serotonin released from sensory neurons may function to modify the immune system in response to changes in the animal's external environment such as the availability, or quality, of food. PMID:24348250

  11. Physical and mathematical models of communication systems

    International Nuclear Information System (INIS)

    Verkhovskaya, E.P.; Yavorskij, V.V.

    2006-01-01

    The theoretical parties connecting resources of communication system with characteristics of channels are received. The model of such systems from positions quasi-classical thermodynamics is considered. (author)

  12. Particle Tracking Model (PTM) with Coastal Modeling System (CMS)

    Science.gov (United States)

    2015-11-04

    Coastal Inlets Research Program Particle Tracking Model (PTM) with Coastal Modeling System ( CMS ) The Particle Tracking Model (PTM) is a Lagrangian...currents and waves. The Coastal Inlets Research Program (CIRP) supports the PTM with the Coastal Modeling System ( CMS ), which provides coupled wave...and current forcing for PTM simulations. CMS -PTM is implemented in the Surface-water Modeling System, a GUI environment for input development

  13. Mitochondrial modulation of phosphine toxicity and resistance in Caenorhabditis elegans.

    Science.gov (United States)

    Zuryn, Steven; Kuang, Jujiao; Ebert, Paul

    2008-03-01

    Phosphine is a fumigant used to protect stored commodities from infestation by pest insects, though high-level phosphine resistance in many insect species threatens the continued use of the fumigant. The mechanisms of toxicity and resistance are not clearly understood. In this study, the model organism, Caenorhabditis elegans, was employed to investigate the effects of phosphine on its proposed in vivo target, the mitochondrion. We found that phosphine rapidly perturbs mitochondrial morphology, inhibits oxidative respiration by 70%, and causes a severe drop in mitochondrial membrane potential (DeltaPsim) within 5 h of exposure. We then examined the phosphine-resistant strain of nematode, pre-33, to determine whether resistance was associated with any changes to mitochondrial physiology. Oxygen consumption was reduced by 70% in these mutant animals, which also had more mitochondrial genome copies than wild-type animals, a common response to reduced metabolic capacity. The mutant also had an unexpected increase in the basal DeltaPsim, which protected individuals from collapse of the membrane potential following phosphine treatment. We tested whether directly manipulating mitochondrial function could influence sensitivity toward phosphine and found that suppression of mitochondrial respiratory chain genes caused up to 10-fold increase in phosphine resistance. The current study confirms that phosphine targets the mitochondria and also indicates that direct alteration of mitochondrial function may be related to phosphine resistance.

  14. Genotypic-specific variance in Caenorhabditis elegans lifetime fecundity.

    Science.gov (United States)

    Diaz, S Anaid; Viney, Mark

    2014-06-01

    Organisms live in heterogeneous environments, so strategies that maximze fitness in such environments will evolve. Variation in traits is important because it is the raw material on which natural selection acts during evolution. Phenotypic variation is usually thought to be due to genetic variation and/or environmentally induced effects. Therefore, genetically identical individuals in a constant environment should have invariant traits. Clearly, genetically identical individuals do differ phenotypically, usually thought to be due to stochastic processes. It is now becoming clear, especially from studies of unicellular species, that phenotypic variance among genetically identical individuals in a constant environment can be genetically controlled and that therefore, in principle, this can be subject to selection. However, there has been little investigation of these phenomena in multicellular species. Here, we have studied the mean lifetime fecundity (thus a trait likely to be relevant to reproductive success), and variance in lifetime fecundity, in recently-wild isolates of the model nematode Caenorhabditis elegans. We found that these genotypes differed in their variance in lifetime fecundity: some had high variance in fecundity, others very low variance. We find that this variance in lifetime fecundity was negatively related to the mean lifetime fecundity of the lines, and that the variance of the lines was positively correlated between environments. We suggest that the variance in lifetime fecundity may be a bet-hedging strategy used by this species.

  15. Characterization of the astacin family of metalloproteases in C. elegans

    Directory of Open Access Journals (Sweden)

    Zapf Richard

    2010-01-01

    Full Text Available Abstract Background Astacins are a large family of zinc metalloproteases found in bacteria and animals. They have diverse roles ranging from digestion of food to processing of extracellular matrix components. The C. elegans genome contains an unusually large number of astacins, of which the majority have not been functionally characterized yet. Results We analyzed the expression pattern of previously uncharacterized members of the astacin family to try and obtain clues to potential functions. Prominent sites of expression for many members of this family are the hypodermis, the alimentary system and several specialized cells including sensory sheath and sockets cells, which are located at openings in the body wall. We isolated mutants affecting representative members of the various subfamilies. Mutants in nas-5, nas-21 and nas-39 (the BMP-1/Tolloid homologue are viable and have no apparent phenotypic defects. Mutants in nas-6 and nas-6; nas-7 double mutants are slow growing and have defects in the grinder of the pharynx, a cuticular structure important for food processing. Conclusions Expression data and phenotypic characterization of selected family members suggest a diversity of functions for members of the astacin family in nematodes. In part this might be due to extracellular structures unique to nematodes.

  16. Gene pathways that delay Caenorhabditis elegans reproductive senescence.

    Directory of Open Access Journals (Sweden)

    Meng C Wang

    2014-12-01

    Full Text Available Reproductive senescence is a hallmark of aging. The molecular mechanisms regulating reproductive senescence and its association with the aging of somatic cells remain poorly understood. From a full genome RNA interference (RNAi screen, we identified 32 Caenorhabditis elegans gene inactivations that delay reproductive senescence and extend reproductive lifespan. We found that many of these gene inactivations interact with insulin/IGF-1 and/or TGF-β endocrine signaling pathways to regulate reproductive senescence, except nhx-2 and sgk-1 that modulate sodium reabsorption. Of these 32 gene inactivations, we also found that 19 increase reproductive lifespan through their effects on oocyte activities, 8 of them coordinate oocyte and sperm functions to extend reproductive lifespan, and 5 of them can induce sperm humoral response to promote reproductive longevity. Furthermore, we examined the effects of these reproductive aging regulators on somatic aging. We found that 5 of these gene inactivations prolong organismal lifespan, and 20 of them increase healthy life expectancy of an organism without altering total life span. These studies provide a systemic view on the genetic regulation of reproductive senescence and its intersection with organism longevity. The majority of these newly identified genes are conserved, and may provide new insights into age-associated reproductive senescence during human aging.

  17. FAMILY OF FLP PEPTIDES IN CAENORHABDITIS ELEGANS AND RELATED NEMATODES

    Directory of Open Access Journals (Sweden)

    Chris eLi

    2014-10-01

    Full Text Available Neuropeptides regulate all aspects of behavior in multicellular organisms. Because of their ability to act at long distances, neuropeptides can exert their effects beyond the conventional synaptic connections, thereby adding an intricate layer of complexity to the activity of neural networks. In the nematode Caenorhabditis elegans, a large number of neuropeptide genes that are expressed throughout the nervous system has been identified. The actions of these peptides supplement the synaptic connections of the 302 neurons, allowing for fine tuning of neural networks and increasing the ways in which behaviors can be regulated. In this review, we focus on a large family of genes encoding FMRFamide-related peptides. These genes, the flp genes, have been used as a starting point to identifying flp genes throughout Nematoda. Nematodes have the largest family of FMRFamide-related peptides described thus far. The challenges in the future are the elucidation of their functions and the identification of the receptors and signaling pathways through which they function.

  18. Two classes of silencing RNAs move between C. elegans tissues

    Science.gov (United States)

    Jose, Antony M; Garcia, Giancarlo A; Hunter, Craig P

    2011-01-01

    Summary Organism-wide RNA interference (RNAi) is due to the transport of mobile silencing RNA throughout the organism but the identities of these mobile RNA species in animals are unknown. Here we present genetic evidence that both the initial double-stranded RNA (dsRNA), which triggers RNAi, and at least one dsRNA intermediate produced during RNAi can act as or generate mobile silencing RNA in Caenorhabditis elegans. This dsRNA intermediate requires the long dsRNA-binding protein RDE-4, the endonuclease DCR-1, which cleaves long dsRNA into double-stranded short-interfering RNA (ds-siRNA), and the putative nucleotidyltransferase MUT-2 (RDE-3). However, single-stranded siRNA and downstream secondary siRNA produced upon amplification by the RNA-dependent RNA Polymerase RRF-1 do not generate mobile silencing RNA. Restricting inter-tissue transport to long dsRNA and directly processed siRNA intermediates rather than amplified siRNA may serve to modulate the extent of systemic silencing in proportion to available dsRNA. PMID:21984186

  19. Response of Caenorhabditis elegans to wireless devices radiation exposure.

    Science.gov (United States)

    Fasseas, Michael K; Fragopoulou, Adamantia F; Manta, Areti K; Skouroliakou, Aikaterini; Vekrellis, Konstantinos; Margaritis, Lukas H; Syntichaki, Popi

    2015-03-01

    To examine the impact of electromagnetic radiation, produced by GSM (Global System for Mobile communications) mobile phones, Wi-Fi (Wireless-Fidelity) routers and wireless DECT (Digital Enhanced Cordless Telecommunications) phones, on the nematode Caenorhabditis elegans. We exposed synchronized populations, of different developmental stages, to these wireless devices at E-field levels below ICNIRP's (International Commission on Non-Ionizing Radiation Protection) guidelines for various lengths of time. WT (wild-type) and aging- or stress-sensitive mutant worms were examined for changes in growth, fertility, lifespan, chemotaxis, short-term memory, increased ROS (Reactive Oxygen Species) production and apoptosis by using fluorescent marker genes or qRT-PCR (quantitative Reverse Transcription-Polymerase Chain Reaction). No statistically significant differences were found between the exposed and the sham/control animals in any of the experiments concerning lifespan, fertility, growth, memory, ROS, apoptosis or gene expression. The worm appears to be robust to this form of (pulsed) radiation, at least under the exposure conditions used.

  20. Using the Model Coupling Toolkit to couple earth system models

    Science.gov (United States)

    Warner, J.C.; Perlin, N.; Skyllingstad, E.D.

    2008-01-01

    Continued advances in computational resources are providing the opportunity to operate more sophisticated numerical models. Additionally, there is an increasing demand for multidisciplinary studies that include interactions between different physical processes. Therefore there is a strong desire to develop coupled modeling systems that utilize existing models and allow efficient data exchange and model control. The basic system would entail model "1" running on "M" processors and model "2" running on "N" processors, with efficient exchange of model fields at predetermined synchronization intervals. Here we demonstrate two coupled systems: the coupling of the ocean circulation model Regional Ocean Modeling System (ROMS) to the surface wave model Simulating WAves Nearshore (SWAN), and the coupling of ROMS to the atmospheric model Coupled Ocean Atmosphere Prediction System (COAMPS). Both coupled systems use the Model Coupling Toolkit (MCT) as a mechanism for operation control and inter-model distributed memory transfer of model variables. In this paper we describe requirements and other options for model coupling, explain the MCT library, ROMS, SWAN and COAMPS models, methods for grid decomposition and sparse matrix interpolation, and provide an example from each coupled system. Methods presented in this paper are clearly applicable for coupling of other types of models. ?? 2008 Elsevier Ltd. All rights reserved.

  1. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  2. The radionuclide migration model in river system

    International Nuclear Information System (INIS)

    Zhukova, O.M.; Shiryaeva, N.M.; Myshkina, M.K.; Shagalova, Eh.D.; Denisova, V.V.; Skurat, V.V.

    2001-01-01

    It was propose the model of radionuclide migration in river system based on principle of the compartmental model at hydraulically stationary and chemically equilibrium conditions of interaction of radionuclides in system water-dredge, water-sediments. Different conditions of radioactive contamination entry in river system were considered. The model was verified on the data of radiation monitoring of Iput' river

  3. CARS microscopy for the monitoring of lipid storage in C. elegans

    Science.gov (United States)

    Enejder, Annika; Brackmann, Christian; Axäng, Claes; Åkeson, Madeleine; Pilon, Marc

    2008-02-01

    After several years of proof-of-principle measurements and focus on technological development, it is timely to make full use of the capabilities of CARS microscopy within the biosciences. We have here identified an urgent biological problem, to which CARS microscopy provides unique insights and consequently may become a widely accepted experimental procedure. In order to improve present understanding of mechanisms underlying dysfunctional metabolism regulation reported for many of our most wide-spread diseases (obesity, diabetes, cardio-vascular diseases etc.), we have monitored genetic and environmental impacts on cellular lipid storage in the model organism C. elegans in vivo in a full-scale biological study. Important advantages of CARS microscopy could be demonstrated compared to present technology, i.e. fluorescence microscopy of labelled lipid stores. The fluorescence signal varies not only with the presence of lipids, but also with the systemic distribution of the fluorophore and the chemical properties of the surrounding medium. By instead probing high-density regions of CH bonds naturally occurring in the sample, the CARS process was shown to provide a consistent representation of the lipid stores. The increased accumulation of lipid stores in mutants with deficiencies in the insulin and transforming growth factor signalling pathways could hereby be visualized and quantified. Furthermore, spectral CARS microscopy measurements in the C-H bond region of 2780-2930 cm -1 provided the interesting observation that this accumulation comes with a shift in the ordering of the lipids from gel- to liquid phase. The present study illustrates that CARS microscopy has a strong potential to become an important instrument for systemic studies of lipid storage mechanisms in living organisms, providing new insights into the phenomena underlying metabolic disorders.

  4. Model Information Exchange System (MIXS).

    Science.gov (United States)

    2013-08-01

    Many travel demand forecast models operate at state, regional, and local levels. While they share the same physical network in overlapping geographic areas, they use different and uncoordinated modeling networks. This creates difficulties for models ...

  5. Towards Modelling of Hybrid Systems

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2006-01-01

    system consists of a number of dynamical systems that are glued together according to information encoded in the discrete part of the system. We develop a definition of a hybrid system as a functor from the category generated by a transition system to the category of directed topological spaces. Its...

  6. Functional genomic analysis of C. elegans molting.

    Directory of Open Access Journals (Sweden)

    Alison R Frand

    2005-10-01

    Full Text Available Although the molting cycle is a hallmark of insects and nematodes, neither the endocrine control of molting via size, stage, and nutritional inputs nor the enzymatic mechanism for synthesis and release of the exoskeleton is well understood. Here, we identify endocrine and enzymatic regulators of molting in C. elegans through a genome-wide RNA-interference screen. Products of the 159 genes discovered include annotated transcription factors, secreted peptides, transmembrane proteins, and extracellular matrix enzymes essential for molting. Fusions between several genes and green fluorescent protein show a pulse of expression before each molt in epithelial cells that synthesize the exoskeleton, indicating that the corresponding proteins are made in the correct time and place to regulate molting. We show further that inactivation of particular genes abrogates expression of the green fluorescent protein reporter genes, revealing regulatory networks that might couple the expression of genes essential for molting to endocrine cues. Many molting genes ar